TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Derlin, Thorsten
A1  - Lapa, Constantin
A1  - Sheikbahaei, Sara
A1  - Higuchi, Takahiro
A1  - Giesel, Frederik L.
A1  - Behr, Spencer
A1  - Drzezga, Alexander
A1  - Kimura, Hiroyuki
A1  - Buck, Andreas K.
A1  - Bengel, Frank M.
A1  - Pomper, Martin G.
A1  - Gorin, Michael A.
A1  - Rowe, Steven P.
T1  - \(^{18}\)F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging
JF  - Theranostics
N2  - Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with \(^{68}\)Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from \(^{68}\)Ga- to \(^{18}\)F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite \(^{68}\)Ge/\(^{68}\)Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, \(^{18}\)F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, \(^{18}\)F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging \(^{18}\)F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available \(^{18}\)F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.
KW  - Radiofluorine
KW  - prostate-specific membrane antigen
KW  - prostate cancer
KW  - \(^{18}\)F
KW  - PSMA
KW  - \(^{68}\)Ga
KW  - theranostics
KW  - radioligand therapy
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202559
SN  - 1838-7640
VL  - 10
IS  - 1
ER  - 
TY  - JOUR
A1  - Lapa, Constantin
A1  - Lückerath, Katharina
A1  - Kleinlein, Irene
A1  - Monoranu, Camelia Maria
A1  - Linsenmann, Thomas
A1  - Kessler, Almuth F.
A1  - Rudelius, Martina
A1  - Kropf, Saskia
A1  - Buck, Andreas K.
A1  - Ernestus, Ralf-Ingo
A1  - Wester, Hans-Jürgen
A1  - Löhr, Mario
A1  - Herrmann, Ken
T1  - \(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma
JF  - Theranostics
N2  - Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor.
15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples.
\(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression.
In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.
KW  - imaging
KW  - chemokine receptor-4
KW  - glioblastoma
KW  - positron emission tomography/computed tomography
KW  - \(^{68}\)Ga-Pentixafor
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168174
VL  - 6
IS  - 3
ER  - 
TY  - INPR
A1  - Werner, Rudolf A.
A1  - Andree, Christian
A1  - Javadi, Mehrbod S.
A1  - Lapa, Constantin
A1  - Buck, Andreas K.
A1  - Higuchi, Takahiro
A1  - Pomper, Martin G.
A1  - Gorin, Michael A.
A1  - Rowe, Steven P.
A1  - Pienta, Kenneth J.
T1  - A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging
T2  - Urology - The Gold Journal
N2  - No abstract available.
KW  - 18F-DCFPyL
KW  - Virchow Node
KW  - PSMA-PET
KW  - Virchow Node
KW  - Positron Emission Tomography
KW  - Prostate Cancer
KW  - PET
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161103
SN  - 0090-4295
N1  - This is the accepted manuscript of Rudolf Werner, Christian Andree, Mehrbod S. Javadi, Constantin Lapa, Andreas K. Buck, Takahiro Higuchi, Martin G. Pomper, Michael A.Gorin, Steven P.Rowe, Kenneth J. Pienta: A Voice From the Past: Re-Discovering the Virchow Node with PSMA-Targeted 18F-DCFPyL PET Imaging. Published in Urology 117(2018), p. 18-21. https://doi.org/10.1016/j.urology.2018.03.030
N1  - Die finale Version dieses Artikels steht unter https://doi.org/10.1016/j.urology.2018.03.030 oder https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-164632 open access zur Verfügung.
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Andree, Christian
A1  - Javadi, Mehrbod S.
A1  - Lapa, Constantin
A1  - Buck, Andreas K.
A1  - Higuchi, Takahiro
A1  - Pomper, Martin G.
A1  - Gorin, Michael A.
A1  - Rowe, Steven P.
A1  - Pienta, Kenneth J.
T1  - A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging
JF  - Urology - The Gold Journal
N2  - No abstract available.
KW  - 18F-DCFPyL
KW  - PET
KW  - PSMA-PET
KW  - Positron Emission Tomography
KW  - Prostate Cancer
KW  - Virchow Node
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164632
SN  - 0090-4295
VL  - 117
ER  - 
TY  - JOUR
A1  - Kosmala, Aleksander
A1  - Serfling, Sebastian E.
A1  - Dreher, Niklas
A1  - Lindner, Thomas
A1  - Schirbel, Andreas
A1  - Lapa, Constantin
A1  - Higuchi, Takahiro
A1  - Buck, Andreas K.
A1  - Weich, Alexander
A1  - Werner, Rudolf A.
T1  - Associations between normal organs and tumor burden in patients imaged with fibroblast activation protein inhibitor-directed positron emission tomography
JF  - Cancers
N2  - (1) Background: We aimed to quantitatively investigate [\(^{68}\)Ga]Ga-FAPI-04 uptake in normal organs and to assess a relationship with the extent of FAPI-avid tumor burden. (2) Methods: In this single-center retrospective analysis, thirty-four patients with solid cancers underwent a total of 40 [\(^{68}\)Ga]Ga-FAPI-04 PET/CT scans. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were established by placing volumes of interest (VOIs) in the heart, liver, spleen, pancreas, kidneys, and bone marrow. Total tumor burden was determined by manual segmentation of tumor lesions with increased uptake. For tumor burden, quantitative assessment included maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA = TV × SUV\(_{mean}\)). Associations between uptake in normal organs and tumor burden were investigated by applying Spearman's rank correlation coefficient. (3) Results: Median SUV\(_{mean}\) values were 2.15 in the pancreas (range, 1.05–9.91), 1.42 in the right (range, 0.57–3.06) and 1.41 in the left kidney (range, 0.73–2.97), 1.2 in the heart (range, 0.46–2.59), 0.86 in the spleen (range, 0.55–1.58), 0.65 in the liver (range, 0.31–2.11), and 0.57 in the bone marrow (range, 0.26–0.94). We observed a trend towards significance for uptake in the myocardium and tumor-derived SUV\(_{max}\) (ρ = 0.29, p = 0.07) and TV (ρ = −0.30, p = 0.06). No significant correlation was achieved for any of the other organs: SUV\(_{max}\) (ρ ≤ 0.1, p ≥ 0.42), TV (ρ ≤ 0.11, p ≥ 0.43), and FTA (ρ ≤ 0.14, p ≥ 0.38). In a sub-analysis exclusively investigating patients with high tumor burden, significant correlations of myocardial uptake with tumor SUV\(_{max}\) (ρ = 0.44; p = 0.03) and tumor-derived FTA with liver uptake (ρ = 0.47; p = 0.02) were recorded. (4) Conclusions: In this proof-of-concept study, quantification of [\(^{68}\)Ga]Ga-FAPI-04 PET showed no significant correlation between normal organs and tumor burden, except for a trend in the myocardium. Those preliminary findings may trigger future studies to determine possible implications for treatment with radioactive FAP-targeted drugs, as higher tumor load or uptake may not lead to decreased doses in the majority of normal organs.
KW  - PET
KW  - [\(^{68}\)Ga]Ga-FAPI
KW  - theranostics
KW  - radioligand therapy
KW  - fibroblast activation protein
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275154
SN  - 2072-6694
VL  - 14
IS  - 11
ER  - 
TY  - JOUR
A1  - Janssen, Jan P.
A1  - Hoffmann, Jan V.
A1  - Kanno, Takayuki
A1  - Nose, Naoko
A1  - Grunz, Jan-Peter
A1  - Onoguchi, Masahisa
A1  - Chen, Xinyu
A1  - Lapa, Constantin
A1  - Buck, Andreas K.
A1  - Higuchi, Takahiro
T1  - Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging
JF  - Scientific Reports
N2  - We aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available \(^{99m}\)Tc-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with \(^{99m}\)Tc-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively. Reconstruction was performed using the similarity-regulated ordered-subsets expectation maximization (SROSEM) algorithm with Gaussian smoothing. Rats were injected with similar to 100 MBq [\(^{99m}\)TcTc-MIBI or similar to 150 MBq [\(^{99m}\)Tc]Tc-HMDP and received multi-frame micro-SPECT imaging after tracer distribution. Animal scans were reconstructed for three different acquisition times and post-processed with different sized Gaussian filters. Following reconstruction, CNR was calculated and image quality evaluated by three independent readers on a five-point scale from 1="very poor" to 5="very good". Point source sensitivity was 567 cps/MBq and radioactive rods as small as 1.2 mm were resolved with the UHR-RM collimator. Collimator-dependent uniformity was 55.5%. Phantom CNR improved with increasing rod size, filter size and activity concentration. Left ventricle and bone structures were successfully visualized in rat experiments. Image quality was strongly affected by the extent of post-filtering, whereas scan time did not have substantial influence on visual assessment. Good image quality was achieved for resolution range greater than 1.8 mm in bone and 2.8 mm in heart. The recently introduced small animal SPECT system with two stationary detectors and UHR-RM collimator is capable to provide excellent image quality in heart and bone scans in a rat using standardized reconstruction parameters and appropriate post-filtering. However, there are still challenges in achieving maximum system resolution in the sub-millimeter range with in vivo settings under limited injection dose and acquisition time.
KW  - small animal SPECT
KW  - HMDP hydroxymethylene diphosphonate
KW  - skeletal
KW  - quality
KW  - scanner
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230616
VL  - 10
ER  - 
TY  - JOUR
A1  - Da Vià, Matteo Claudio
A1  - Solimando, Antonio Giovanni
A1  - Garitano-Trojaola, Andoni
A1  - Barrio, Santiago
A1  - Munawar, Umair
A1  - Strifler, Susanne
A1  - Haertle, Larissa
A1  - Rhodes, Nadine
A1  - Vogt, Cornelia
A1  - Lapa, Constantin
A1  - Beilhack, Andreas
A1  - Rasche, Leo
A1  - Einsele, Hermann
A1  - Kortüm, K. Martin
T1  - CIC Mutation as a Molecular Mechanism of Acquired Resistance to Combined BRAF‐MEK Inhibition in Extramedullary Multiple Myeloma with Central Nervous System Involvement
JF  - The Oncologist
N2  - Combined MEK‐BRAF inhibition is a well‐established treatment strategy in BRAF‐mutated cancer, most prominently in malignant melanoma with durable responses being achieved through this targeted therapy. However, a subset of patients face primary unresponsiveness despite presence of the activating mutation at position V600E, and others acquire resistance under treatment. Underlying resistance mechanisms are largely unknown, and diagnostic tests to predict tumor response to BRAF‐MEK inhibitor treatment are unavailable.

Multiple myeloma represents the second most common hematologic malignancy, and point mutations in BRAF are detectable in about 10% of patients. Targeted inhibition has been successfully applied, with mixed responses observed in a substantial subset of patients mirroring the widespread spatial heterogeneity in this genomically complex disease. Central nervous system (CNS) involvement is an extremely rare, extramedullary form of multiple myeloma that can be diagnosed in less than 1% of patients. It is considered an ultimate high‐risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases. Here we not only describe the first patient with an extramedullary CNS relapse responding to targeted dabrafenib and trametinib treatment, we furthermore provide evidence that a point mutation within the capicua transcriptional repressor (CIC) gene mediated the acquired resistance in this patient.
KW  - Multiple myeloma
KW  - Extramedullary disease
KW  - Capicua transcriptional repressor
KW  - Drug resistance
KW  - BRAF mutation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219549
VL  - 25
IS  - 2
ER  - 
TY  - JOUR
A1  - Toyama, Yoshitaka
A1  - Werner, Rudolf A.
A1  - Ruiz-Bedoya, Camilo A.
A1  - Ordonez, Alvaro A.
A1  - Takase, Kei
A1  - Lapa, Constantin
A1  - Jain, Sanjay K.
A1  - Pomper, Martin G.
A1  - Rowe, Steven P.
A1  - Higuchi, Takahiro
T1  - Current and future perspectives on functional molecular imaging in nephro-urology: theranostics on the horizon
JF  - Theranostics
N2  - In recent years, a paradigm shift from single-photon-emitting radionuclide radiotracers toward positron-emission tomography (PET) radiotracers has occurred in nuclear oncology. Although PET-based molecular imaging of the kidneys is still in its infancy, such a trend has emerged in the field of functional renal radionuclide imaging. Potentially allowing for precise and thorough evaluation of renal radiotracer urodynamics, PET radionuclide imaging has numerous advantages including precise anatomical co-registration with CT images and dynamic three-dimensional imaging capability. In addition, relative to scintigraphic approaches, PET can allow for significantly reduced scan time enabling high-throughput in a busy PET practice and further reduces radiation exposure, which may have a clinical impact in pediatric populations. In recent years, multiple renal PET radiotracers labeled with C-11, Ga-68, and F-18 have been utilized in clinical studies. Beyond providing a precise non-invasive read-out of renal function, such radiotracers may also be used to assess renal inflammation. This manuscript will provide an overview of renal molecular PET imaging and will highlight the transformation of conventional scintigraphy of the kidneys toward novel, high-resolution PET imaging for assessing renal function. In addition, future applications will be introduced, e.g. by transferring the concept of molecular image-guided diagnostics and therapy (theranostics) to the field of nephrology.
KW  - glomerular filtration rate
KW  - renal
KW  - kidney
KW  - renal function
KW  - positron emission tomography
KW  - nephrology
KW  - urology
KW  - molecular imaging
KW  - theranostics
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260090
VL  - 11
IS  - 12
ER  - 
TY  - JOUR
A1  - Lapa, Constantin
A1  - Herrmann, Ken
A1  - Schirbel, Andreas
A1  - Hänscheid, Heribert
A1  - Lückerath, Katharina
A1  - Schottelius, Margret
A1  - Kircher, Malte
A1  - Werner, Rudolf A.
A1  - Schreder, Martin
A1  - Samnick, Samuel
A1  - Kropf, Saskia
A1  - Knop, Stefan
A1  - Buck, Andreas K.
A1  - Einsele, Hermann
A1  - Wester, Hans-Juergen
A1  - Kortüm, K. Martin
T1  - CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma
JF  - Theranostics
N2  - C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM).

Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival.

ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive.

CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted.
KW  - medicine
KW  - multiple myeloma
KW  - PET
KW  - CXCR4
KW  - theranostics
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172095
VL  - 7
IS  - 6
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Kircher, Stefan
A1  - Higuchi, Takahiro
A1  - Kircher, Malte
A1  - Schirbel, Andreas
A1  - Wester, Hans-Jürgen
A1  - Buck, Andreas K.
A1  - Pomper, Martin G.
A1  - Rowe, Steven P.
A1  - Lapa, Constantin
T1  - CXCR4-directed imaging in solid tumors
JF  - Frontiers in Oncology
N2  - Despite histological evidence in various solid tumor entities, available experience with CXCR4-directed diagnostics and endoradiotherapy mainly focuses on hematologic diseases. With the goal of expanding the application of CXCR4 theranostics to solid tumors, we aimed to elucidate the feasibility of CXCR4-targeted imaging in a variety of such neoplasms.
Methods: Nineteen patients with newly diagnosed, treatment-naïve solid tumors including pancreatic adenocarcinoma or neuroendocrine tumor, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and prostate cancer underwent [\(^{68}\)Ga]Pentixafor PET/CT. CXCR4-mediated uptake was assessed both visually and semi-quantitatively by evaluation of maximum standardized uptake values (SUV\(_{max}\)) of both primary tumors and metastases. With physiologic liver uptake as reference, tumor-to-background ratios (TBR) were calculated. [\(^{68}\)Ga]Pentixafor findings were further compared to immunohistochemistry and [\(^{18}\)F]FDG PET/CT.
Results: On [\(^{68}\)Ga]Pentixafor PET/CT, 10/19 (52.6%) primary tumors were visually detectable with a median SUVmax of 5.4 (range, 1.7–16.0) and a median TBR of 2.6 (range, 0.8–7.4), respectively. The highest level of radiotracer uptake was identified in a patient with cholangiocarcinoma (SUVmax, 16.0; TBR, 7.4). The relatively low uptake on [\(^{68}\)Ga]Pentixafor was also noted in metastases, exhibiting a median SUVmax of 4.5 (range, 2.3–8.8; TBR, 1.7; range, 1.0–4.1). A good correlation between uptake on [\(^{68}\)Ga]Pentixafor and histological derived CXCR4 expression was noted (R = 0.62, P < 0.05). In the 3 patients in whom [\(^{18}\)F]FDG PET/CT was available, [\(^{68}\)Ga]Pentixafor exhibited lower uptake in all lesions.
Conclusions: In this cohort of newly diagnosed, treatment-naïve patients with solid malignancies, CXCR4 expression as detected by [\(^{68}\)Ga]Pentixafor-PET/CT and immunohistochemistry was rather moderate. Thus, CXCR4-directed imaging may not play a major role in the management of solid tumors in the majority of patients.
KW  - CXCR4
KW  - [68Ga]Pentixafor
KW  - theranostics
KW  - solid tumors
KW  - chemokine receptor
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195678
SN  - 2234-943X
VL  - 9
IS  - 770
ER  - 
TY  - JOUR
A1  - Weich, Alexander
A1  - Werner, Rudolf A.
A1  - Buck, Andreas K.
A1  - Hartrampf, Philipp E.
A1  - Serfling, Sebastian E.
A1  - Scheurlen, Michael
A1  - Wester, Hans-Jürgen
A1  - Meining, Alexander
A1  - Kircher, Stefan
A1  - Higuchi, Takahiro
A1  - Pomper, Martin G.
A1  - Rowe, Steven P.
A1  - Lapa, Constantin
A1  - Kircher, Malte
T1  - CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas
JF  - Diagnostics
N2  - We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.
KW  - CXCR4
KW  - NET
KW  - NEC
KW  - <sup>68</sup>Ga-Pentixafor
KW  - <sup>18</sup>F-FDG
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234231
SN  - 2075-4418
VL  - 11
IS  - 4
ER  - 
TY  - JOUR
A1  - Brumberg, Joachim
A1  - Kuzkina, Anastasia
A1  - Lapa, Constantin
A1  - Mammadova, Sona
A1  - Buck, Andreas
A1  - Volkmann, Jens
A1  - Sommer, Claudia
A1  - Isaias, Ioannis U.
A1  - Doppler, Kathrin
T1  - Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy
JF  - Neurobiology of Disease
N2  - Pathological aggregates of alpha-synuclein in peripheral dermal nerve fibers can be detected in patients with idiopathic Parkinson's disease and multiple system atrophy. This study combines skin biopsy staining for p-alpha-synuclein depositions and radionuclide imaging of the heart with [\(^{123}\)I]-metaiodobenzylguanidine to explore peripheral denervation in both diseases. To this purpose, 42 patients with a clinical diagnosis of Parkinson's disease or multiple system atrophy were enrolled. All patients underwent a standardized clinical workup including neurological evaluation, neurography, and blood samples. Skin biopsies were obtained from the distal and proximal leg, back, and neck for immunofluorescence double labeling with anti-p-alpha-synuclein and anti-PGP9.5. All patients underwent myocardial [\(^{123}\)I]-metaiodobenzylguanidine scintigraphy. Dermal p-alpha-synuclein was observed in 47.6% of Parkinson's disease patients and was mainly found in autonomic structures. 81.0% of multiple system atrophy patients had deposits with most of cases in somatosensory fibers. The [\(^{123}\)I]-metaiodobenzylguanidine heart-to-mediastinum ratio was lower in Parkinson's disease than in multiple system atrophy patients (1.94 +/- 0.63 vs. 2.91 +/- 0.96; p < 0.0001). Irrespective of the diagnosis, uptake was lower in patients with than without p-alpha-synuclein in autonomic structures (1.42 +/- 0.51 vs. 2.74 +/- 0.83; p < 0.0001). Rare cases of Parkinson's disease with p-alpha-synuclein in somatosensory fibers and multiple system atrophy patients with deposits in autonomic structures or both fiber types presented with clinically overlapping features. In conclusion, this study suggests that alpha-synuclein contributes to peripheral neurodegeneration and mediates the impairment of cardiac sympathetic neurons in patients with synucleinopathies. Furthermore, it indicates that Parkinson's disease and multiple system atrophy share pathophysiologic mechanisms of peripheral nervous system dysfunction with a clinical overlap.
KW  - peripheral nervous system
KW  - Parkinson's disease
KW  - skin biopsy
KW  - MIBG scintigraphy
KW  - multiple system atrophy
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260061
VL  - 153
ER  - 
TY  - JOUR
A1  - Brumberg, Joachim
A1  - Beckl, Melanie
A1  - Dierks, Alexander
A1  - Schirbel, Andreas
A1  - Krebs, Markus
A1  - Buck, Andreas
A1  - Kübler, Hubert
A1  - Lapa, Constantin
A1  - Seitz, Anna Katharina
T1  - Detection Rate of \(^{68}\)Ga-PSMA Ligand PET/CT in Patients with Recurrent Prostate Cancer and Androgen Deprivation Therapy
JF  - Biomedicines
N2  - Prostate-specific membrane antigen (PSMA) ligand PET/CT enables the localization of tumor lesions in patients with recurrent prostate cancer, but it is unclear whether androgen deprivation therapy (ADT) influences diagnostic accuracy. The aim of this study was to evaluate the effect of ADT on the detection rate of \(^{68}\)Ga-PSMA ligand PET/CT. Thus, 399 patients with initial radical prostatectomy and 68Ga-PSMA ligand PET/CT during PSA relapse were retrospectively evaluated. Propensity score matching was used to create two balanced groups of 62 subjects who either did or did not receive ADT within six months before imaging. All \(^{68}\)Ga-PSMA ligand PET/CT were evaluated visually and with semiquantitative measures. The detection rate of tumor recurrence was significantly higher in the group with ADT (88.7% vs. 72.6%, p = 0.02) and improved with increasing PSA-levels in both groups. In subjects with pathological PET/CT and ADT, whole-body total lesion PSMA (p < 0.01) and PSMA-derived tumor volume (p < 0.01) were significantly higher than in those without ADT. More PSMA-positive lesions and higher PSMA-derived volumetric parameters in patients with ADT suggest that a better detection rate is related to a (biologically) more advanced disease stage. Due to high detection rates in patients with PSA-levels < 2 ng/mL, the withdrawal of ADT before PSMA ligand PET/CT cannot be recommended.
KW  - 68Ga-PSMA ligand PET/CT
KW  - androgen deprivation therapy
KW  - detection rate
KW  - recurrent prostate cancer
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219301
SN  - 2227-9059
VL  - 8
IS  - 11
ER  - 
TY  - JOUR
A1  - Hartrampf, Philipp E.
A1  - Lapa, Constantin
A1  - Serfling, Sebastian E.
A1  - Buck, Andreas K.
A1  - Seitz, Anna Katharina
A1  - Meyer, Philipp T.
A1  - Ruf, Juri
A1  - Michalski, Kerstin
T1  - Development of Discordant Hypermetabolic Prostate Cancer Lesions in the Course of [\(^{177}\)Lu]PSMA Radioligand Therapy and Their Possible Influence on Patient Outcome
JF  - Cancers
N2  - Simple Summary
Discordant FDG-positive but PSMA-negative (FDG+/PSMA−) metastases constitute a negative prognostic marker of overall survival in patients undergoing PSMA radioligand therapy (RLT). The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions, which occur during or after PSMA RLT. In a retrospective bicentric analysis of 32 patients undergoing PSMA RLT and follow-up dual tracer staging with PSMA and FDG PET/CT, FDG+/PSMA− lesions occurred in a limited number of patients. However, the presence of FDG+/PSMA− lesions appears not to have a significant impact on the OS, but further studies are needed to establish the clinical relevance of such lesions.

Abstract
Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate-specific membrane antigen (PSMA) is crucial for the assessment of adequate PSMA expression in patients with metastatic castration-resistant prostate cancer (mCRPC) prior to PSMA radioligand therapy (PSMA RLT). Moreover, initial dual tracer staging using combined PSMA and [\(^{18}\)F]fluorodeoxyglucose (FDG) PET/CT provides relevant information, since discordant FDG-positive but PSMA-negative (FDG+/PSMA−) lesions constitute a negative prognostic marker of overall survival (OS) after PSMA RLT. However, little is known about the prognostic implications of dual tracer imaging for restaging at follow-up. The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions during or after PSMA RLT. Methods: This bicentric analysis included 32 patients with mCRPC who underwent both FDG and PSMA PET/CT imaging after two or four cycles of PSMA RLT. Patients with FDG+/PSMA− lesions prior to PSMA RLT were not considered. The presence of FDG+/PSMA− lesions was assessed with follow-up dual tracer imaging of patients after two or four cycles of PSMA RLT. Patients with at least one new FDG+/PSMA− lesion were compared to patients without any FDG+/PSMA− lesions at the respective time points. A log-rank analysis was used to assess the difference in OS between subgroups. Results: After two cycles of PSMA RLT, four of 32 patients (13%) had FDG+/PSMA− metastases. No significant difference in OS was observed (p = 0.807), as compared to patients without FDG+/PSMA− lesions. Follow-up dual tracer imaging after the 4th cycle of PSMA RLT was available in 18 patients. Of these, four patients presented with FDG+/PSMA− findings (n = 2 already after two cycles). After the fourth cycle of PSMA RLT, no significant difference in OS was observed between patients with and without FDG+/PSMA− lesions (p = 0.442). Conclusion: This study shows that FDG+/PSMA− lesions develop in a limited number of patients undergoing PSMA RLT. Further studies are needed to establish the clinical relevance of such lesions.
KW  - PSMA
KW  - FDG
KW  - PET/CT
KW  - prostate cancer
KW  - radioligand therapy
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245168
SN  - 2072-6694
VL  - 13
IS  - 17
ER  - 
TY  - CHAP
A1  - Werner, Rudolf A.
A1  - Marcus, Charles
A1  - Sheikhbahaei, Sara
A1  - Higuchi, Takahiro
A1  - Solnes, Lilja B.
A1  - Rowe, Steven P.
A1  - Buck, Andreas K.
A1  - Lapa, Constantin
A1  - Javadi, Mehrbod S.
T1  - Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method
T2  - Journal of Nuclear Medicine
N2  - No abstract available.
KW  - Parkinson-Krankheit
KW  - SPECT
KW  - Parkinson
KW  - Parkinson Disease
KW  - DaTscan
KW  - Ioflupane
KW  - molecular imaging
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162208
UR  - http://jnm.snmjournals.org/content/59/supplement_1/626.abstract
SN  - 0161-5505
N1  - This research was originally published in JNM. Rudolf A. Werner, Charles Marcus, Sara Sheikhbahaei, Takahiro Higuchi, Lilja B. Solnes, Steven P. Rowe, Andreas K. Buck, Constantin Lapa, Mehrbod S. Javadi. Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method. J Nucl Med. May 1, 2018; vol. 59 no. supplement 1:626. © SNMMI.
VL  - 59
IS  - Supplement No. 1
SP  - 626
ER  - 
TY  - JOUR
A1  - Brumberg, Joachim
A1  - Schröter, Nils
A1  - Blazhenets, Ganna
A1  - Frings, Lars
A1  - Volkmann, Jens
A1  - Lapa, Constantin
A1  - Jost, Wolfgang H.
A1  - Isaias, Ioannis U.
A1  - Meyer, Philipp T.
T1  - Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy
JF  - NPJ Parkinsons Disease
N2  - [\(^{18}\)F]fluorodeoxyglucose (FDG) PET and [\(^{123}\)I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 +/- 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson's disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred.
KW  - clinical diagnosis
KW  - F-18-FDG PET
KW  - disease
KW  - dementia
KW  - accuracy
KW  - stimulation
KW  - guidelines
KW  - criteria
KW  - brain
KW  - risk
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230675
VL  - 6
ER  - 
TY  - JOUR
A1  - Schumann, Sarah
A1  - Scherthan, Harry
A1  - Frank, Torsten
A1  - Lapa, Constantin
A1  - Müller, Jessica
A1  - Seifert, Simone
A1  - Lassmann, Michael
A1  - Eberlein, Uta
T1  - DNA Damage in Blood Leukocytes of Prostate Cancer Patients Undergoing PET/CT Examinations with [\(^{68}\)Ga]Ga-PSMA I&T
JF  - Cancers
N2  - The aim was to investigate the induction and repair of radiation-induced DNA double-strand breaks (DSBs) as a function of the absorbed dose to the blood of patients undergoing PET/CT examinations with [68Ga]Ga-PSMA. Blood samples were collected from 15 patients before and at four time points after [68Ga]Ga-PSMA administration, both before and after the PET/CT scan. Absorbed doses to the blood were calculated. In addition, blood samples with/without contrast agent from five volunteers were irradiated ex vivo by CT while measuring the absorbed dose. Leukocytes were isolated, fixed, and stained for co-localizing γ-H2AX+53BP1 DSB foci that were enumerated manually. In vivo, a significant increase in γ-H2AX+53BP1 foci compared to baseline was observed at all time points after administration, although the absorbed dose to the blood by 68Ga was below 4 mGy. Ex vivo, the increase in radiation-induced foci depended on the absorbed dose and the presence of contrast agent, which could have caused a dose enhancement. The CT-dose contribution for the patients was estimated at about 12 mGy using the ex vivo calibration. The additional number of DSB foci induced by CT, however, was comparable to the one induced by 68Ga. The significantly increased foci numbers after [68Ga]Ga-PSMA administration may suggest a possible low-dose hypersensitivity.
KW  - DNA double-strand breaks
KW  - γ-H2AX
KW  - 53BP1
KW  - nuclear medicine
KW  - dosimetry
KW  - Ga-68
KW  - PSMA
KW  - PET/CT
KW  - contrast agent
KW  - prostate cancer
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200585
SN  - 2072-6694
VL  - 12
IS  - 2
ER  - 
TY  - JOUR
A1  - Kläsner, Benjamin
A1  - Buchmann, Niels
A1  - Gempt, Jens
A1  - Ringel, Florian
A1  - Lapa, Constantin
A1  - Krause, Bernd Joachim
T1  - Early [\(^{18}\)F]FET-PET in Gliomas after Surgical Resection: Comparison with MRI and Histopathology
JF  - PLoS One
N2  - Background The precise definition of the post-operative resection status in high-grade gliomas (HGG) is crucial for further management. We aimed to assess the feasibility of assessment of the resection status with early post-operative positron emission tomography (PET) using [\(^{18}\)F]O-(2-[\(^{18}\)F]-fluoroethyl)-L-tyrosine ([\(^{18}\)F]FET). Methods 25 patients with the suspicion of primary HGG were enrolled. All patients underwent preoperative [\(^{18}\)F]FET-PET and magnetic resonance imaging (MRI). Intra-operatively, resection status was assessed using 5-aminolevulinic acid (5-ALA). Imaging was repeated within 72h after neurosurgery. Post-operative [\(^{18}\)F]FET-PET was compared with MRI, intra-operative assessment and clinical follow-up. Results [\(^{18}\)F]FET-PET, MRI and intra-operative assessment consistently revealed complete resection in 12/25 (48%) patients and incomplete resection in 6/25 cases (24%). In 7 patients, PET revealed discordant findings. One patient was re-resected. 3/7 experienced tumor recurrence, 3/7 died shortly after brain surgery. Conclusion Early assessment of the resection status in HGG with [\(^{18}\)F]FET-PET seems to be feasible.
KW  - glioblastoma multiforme
KW  - brain tumors
KW  - C-11-methionine pet
KW  - positron-emission-tomography
KW  - improves
KW  - survival
KW  - delineation
KW  - radiotherapy
KW  - methionine pet
KW  - cerebral gliomas
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139549
VL  - 10
IS  - 10
ER  - 
TY  - CHAP
A1  - Werner, Rudolf
A1  - Kobayashi, Ryohei
A1  - Wakabayashi, Hiroshi
A1  - Lapa, Constantin
A1  - Menke, Andreas
A1  - Higuchi, Takahiro
T1  - Effect of Antidepressants on Radiolabeled Metaiodobenzylguanidine (MIBG) Uptake
T2  - European Heart Journal - Cardiovascular Imaging
N2  - No abstract available.
KW  - MIBG
KW  - Metaiodobenzylguanidine
KW  - mIBG
KW  - antidepressants
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161116
SN  - 2047-2404
N1  - This is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal Cardiovascular Imaging following peer review. The version of 
record Eur Heart J Cardiovasc Imaging. ISSN: 2047-2404. Supplement, vol. 18, i52-53, May 2017 is available online at: 10.1093/ehjci/jex080.
VL  - 18
IS  - Supplement
PB  - Oxford University Press
ER  - 
TY  - INPR
A1  - Yin, Yafu
A1  - Werner, Rudolf A.
A1  - Higuchi, Takahiro
A1  - Lapa, Constantin
A1  - Pienta, Kenneth J.
A1  - Pomper, Martin G.
A1  - Gorin, Michael A.
A1  - Rowe, Steven P.
T1  - Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMARADS- 3B Categories
T2  - Journal of Nuclear Medicine
N2  - Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has become commonly utilized in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa.
Methods: PET/CT imaging with \(^{18}\)F-DCFPyL was carried out in 110 patients with PCa and lesions were categorized according to PSMA-RADS Version 1.0. 56/110 (50.9%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions and 22/56 (39.3%) patients had adequate follow-up to be included in the analysis. The maximum standardized uptake values (SUV\(_{max}\)) of the lesions were obtained and the ratios of SUV\(_{max}\) of the lesions to SUV\(_{mean}\) of blood pool (SUV\(_{max}\)-lesion/SUV\(_{mean}\)-bloodpool) were calculated. Pre-determined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine if they demonstrated evidence of underlying malignancy.
Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were evaluable on follow-up imaging. 27/46 (58.7%) lesions demonstrated changes on follow-up imaging consistent with the presence of underlying PCa at baseline. These lesions included 24/32 (75.0%) PSMA-RADS-3A lesions and 3/14 (21.4%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up.
Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and this information should be taken into when guiding patient therapy.
KW  - PSMA-RADS-3B
KW  - Positronen-Emissions-Tomografie
KW  - prostate-specific membrane antigen
KW  - prostate cancer
KW  - PSMA-targeted PET
KW  - PSMA-RADS-3A
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167594
SN  - 0161-5505
N1  - This research was originally published in JNM. Yafu Yin, Rudolf A. Werner, Takahiro Higuchi, Constantin Lapa, Kenneth J. Pienta, Martin G. Pomper, Michael A. Gorin, Steven P. Rowe.
Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMA-RADS-3B Categories. J Nucl Med. 2019;60:511-516 © SNMMI.
ER  - 
TY  - JOUR
A1  - Werner, Rudolf
A1  - Wakabyashi, Hiroshi
A1  - Chen, Xinyu
A1  - Hirano, Mitsuru
A1  - Shinaji, Tetsuya
A1  - Lapa, Constantin
A1  - Rowe, Steven
A1  - Javadi, Mehrbod
A1  - Higuchi, Takahiro
T1  - Functional renal imaging with \(^{18}\)F-FDS PET in rat models of renal disorders
JF  - Journal of Nuclear Medicine
N2  - Background: Precise regional quantitative assessment of renal function is limited with conventional \(^{99m}\)Tc-labeled renal radiotracers. A recent study reported that the positron emission tomography (PET) radiotracer 2-deoxy-2-(\(^{18}\)F-fluorosorbitol (\(^{18}\)F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, (\(^{18}\)F-FDS is available via simple reduction from routinely used 2-deoxy-2-(\(^{18}\)F-fluoro-D-glucose ((\(^{18}\)F-FDG). We aimed to further investigate the potential of (\(^{18}\)F-FDS PET as a functional renal imaging agent using rat models of kidney diseases. 
Methods: Two different rat models of renal impairment were investigated: Glycerol induced acute renal failure (ARF) by intramuscular administration of glycerol in hind legs and unilateral ureteral obstruction (UUO) by ligation of the left ureter. 24h after these treatments, dynamic 30 min 18F-FDS PET data were acquired using a dedicated small animal PET system. Urine 18F-FDS radioactivity 30 min after radiotracer injection was measured together with co-injected \(^{99m}\)Tc-diethylenetriaminepentaacetic acid (\(^{99m}\)Tc-DTPA) urine activity. Results: Dynamic PET imaging demonstrated rapid (\(^{18}\)F-FDS accumulation in the renal cortex and rapid radiotracer excretion via kidneys in control healthy rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in ARF rats and UUO-treated kidneys. Measured urine radiotracer concentrations of (\(^{18}\)F-FDS and \(^{99m}\)Tc-DTPA were well correlated (R=0.84, P<0.05). 
Conclusions: (\(^{18}\)F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. Advantages of high spatiotemporal resolution of PET imaging and simple tracer production could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.
KW  - unilateral ureteral obstruction
KW  - Nierenfunktionsstörung
KW  - Positronen-Emissions-Tomografie
KW  - 18F-FDS
KW  - 99mTc-DTPA
KW  - PET
KW  - renal failure
KW  - Glomerular filtration
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161279
SN  - 0161-5505
N1  - This research was originally published in JNM. Rudolf A. Werner, Hiroshi Wakabayashi, Xinyu Chen, Mitsuru Hirano, Tetsuya Shinaji, Constantin Lapa, Steven P. Rowe, Mehrbod S. Javadi and Takahiro Higuchi. Functional renal imaging with 18F-FDS PET in rat models of renal disorders. J Nucl Med. May 1, 2018;vol. 59 no. 5: 828-832. © SNMMI.
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Habacha, Bilêl
A1  - Lütje, Susanne
A1  - Bundschuh, Lena
A1  - Higuchi, Takahiro
A1  - Hartrampf, Philipp
A1  - Serfling, Sebastian E.
A1  - Derlin, Thorsten
A1  - Lapa, Constantin
A1  - Buck, Andreas K.
A1  - Essler, Markus
A1  - Pienta, Kenneth J.
A1  - Eisenberger, Mario A.
A1  - Markowski, Mark C.
A1  - Shinehouse, Laura
A1  - AbdAllah, Rehab
A1  - Salavati, Ali
A1  - Lodge, Martin A.
A1  - Pomper, Martin G.
A1  - Gorin, Michael A.
A1  - Bundschuh, Ralph A.
A1  - Rowe, Steven P.
T1  - High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with \(^{18}\)F-DCFPyL
JF  - Molecular Imaging
N2  - No abstract available.
KW  - SUV
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300748
VL  - 2022
ER  - 
TY  - JOUR
A1  - Brumberg, Joachim
A1  - Blazhenets, Ganna
A1  - Schröter, Nils
A1  - Frings, Lars
A1  - Jost, Wolfgang H.
A1  - Lapa, Constantin
A1  - Meyer, Philipp T.
T1  - Imaging cardiac sympathetic innervation with MIBG: linear conversion of the heart-to-mediastinum ratio between different collimators
JF  - EJNMMI Physics
N2  - Background
The heart-to-mediastinum (H/M) ratio is a commonly used parameter to measure cardiac I-123 metaiodobenzylguanidine (MIBG) uptake. Since the H/M ratio is substantially influenced by the collimator type, we investigated whether an empirical linear conversion of H/M ratios between camera systems with low-energy (LE) and medium-energy (ME) collimator is possible.

Methods
We included 18 patients with parkinsonism who were referred to one of the two participating molecular imaging facilities for the evaluation of cardiac sympathetic innervation by MIBG scintigraphy. Two consecutive planar image datasets were acquired with LE and ME collimators at 4 h after MIBG administration. Linear regression analyses were performed to describe the association between the H/M ratios gained with both collimator settings, and the accuracy of a linear transfer of the H/M ratio between collimators and across centers was assessed using a leave-one-out procedure.

Results
H/M ratios acquired with LE and ME collimators showed a strong linear relationship both within each imaging facility (R\(^2\) = 0.99, p < 0.001 and R\(^2\) = 0.90, p < 0.001) and across centers (H/M-LE = 0.41 × H/M-ME + 0.63, R\(^2\) = 0.97, p < 0.001). A linear conversion of H/M ratios between collimators and across centers was estimated to be very accurate (mean absolute error 0.05 ± 0.04; mean relative absolute error 3.2 ± 2.6%).

Conclusions
The present study demonstrates that a simple linear conversion of H/M ratios acquired with different collimators is possible with high accuracy. This should greatly facilitate the exchange of normative data between settings and pooling of data from different institutions.
KW  - MIBG
KW  - collimator
KW  - heart-to-mediastinum ratio
KW  - linear conversion
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221675
VL  - 6
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Weich, Alexander
A1  - Higuchi, Takahiro
A1  - Schmid, Jan S.
A1  - Schirbel, Andreas
A1  - Lassmann, Michael
A1  - Wild, Vanessa
A1  - Rudelius, Martina
A1  - Kudlich, Theodor
A1  - Herrmann, Ken
A1  - Scheurlen, Michael
A1  - Buck, Andreas K.
A1  - Kropf, Saskia
A1  - Wester, Hans-Jürgen
A1  - Lapa, Constantin
T1  - Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach
JF  - Theranostics
N2  - C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.
KW  - SSTR
KW  - peptide receptor radionuclide therapy
KW  - neuroendocrine tumor
KW  - [\(^{68}\)Ga]Pentixafor
KW  - CXCR4
KW  - chemokine receptor
KW  - PET/CT
KW  - DOTATOC
KW  - PRRT
KW  - Positronen-Emissions-Tomografie
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158008
VL  - 7
IS  - 6
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Kobayashi, Ryohei
A1  - Javadi, Mehrbod Som
A1  - Köck, Zoe
A1  - Wakabayashi, Hiroshi
A1  - Unterecker, Stefan
A1  - Nakajima, Kenichi
A1  - Lapa, Constantin
A1  - Menke, Andreas
A1  - Higuchi, Takahiro
T1  - Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits
JF  - Journal of Nuclear Medicine
N2  - Background: \(^{123}\)I-metaiodobenzylguanidine (mIBG) provides independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not impact its quantitative information. We aimed to evaluate the four most-prescribed antidepressants currently used as a first‑line treatment for patients with major depressive disorder (MDD) and their potential on altering mIBG imaging results. 
Methods: The inhibition effect of four different types of antidepressants (desipramine, escitalopram, venlafaxine and bupropion) for MDD treatment on \(^{131}\)I-mIBG uptake was assessed by in-vitro cell uptake assays using human neuroblastoma SK-N-SH cells. The half maximal inhibitory concentration (IC50) of tracer uptake was determined from dose-response curves. To evaluate the effects of IV pretreatment with desipramine (1.5 mg/kg) and escitalopram (2.5, 15 mg/kg) on mIBG cardiac uptake, in-vivo planar 123I-mIBG scans in healthy New Zealand White Rabbits were conducted. Results: The IC50 values of desipramine, escitalopram, venlafaxine and bupropion on \(^{131}\)I-mIBG cellular uptake were 11.9 nM, 7.5 μM, 4.92 μM, and 12.9 μM, respectively. At the maximum serum concentration (Cmax, as derived by previous clinical trials), the inhibition rates of 131I-mIBG uptake were 90.6 % for desipramine, 25.5 % for venlafaxine, 11.7 % for bupropion and 0.72 % for escitalopram. A low inhibition rate for escitalopram in the cell uptake study triggered investigation of an in-vivo rabbit model: with dosage considerably higher than clinical practice, the non-inhibitory effect of escitalopram was confirmed. Furthermore, pretreatment with desipramine led to a marked reduction of cardiac 123I-mIBG uptake. 
Conclusions: In the present in-vitro binding assay and in-vivo rabbit study, the selective-serotonin reuptake inhibitor escitalopram had no major impact on neuronal cardiac mIBG uptake within therapeutic dose ranges, while other types of first-line antidepressants for MDD treatment led to a significant decrease. These preliminary results warrant further confirmatory clinical trials regarding the reliability of cardiac mIBG imaging, in particular, if the patient’s neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine interfering antidepressant.
KW  - MDD
KW  - Antidepressants
KW  - depression
KW  - 123I-mIBG
KW  - antidepressant
KW  - cardiac sympathetic nerve system
KW  - major depressive disorder
KW  - myocardial sympathetic innervation imaging
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161280
SN  - 0161-5505
N1  - This research was originally published in JNM. Rudolf A. Werner, Ryohei Kobayashi, Mehrbod Som Javadi, Zoe Köck, Hiroshi Wakabayashi, Stefan Unterecker, Kenichi Nakajima, Constantin Lapa, Andreas Menke, Takahiro Higuchi. Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits. J. Nucl. Med. July 1, 2018, vol. 59, no. 7, 1099-1103. © SNMMI.
ER  - 
TY  - JOUR
A1  - Serfling, Sebastian E.
A1  - Lapa, Constantin
A1  - Dreher, Niklas
A1  - Hartrampf, Philipp E.
A1  - Rowe, Steven P.
A1  - Higuchi, Takahiro
A1  - Schirbel, Andreas
A1  - Weich, Alexander
A1  - Hahner, Stefanie
A1  - Fassnacht, Martin
A1  - Buck, Andreas K.
A1  - Werner, Rudolf A.
T1  - Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT
JF  - Molecular Imaging and Biology
N2  - Background
CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs.

Methods
Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV\(_{mean}\) x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden.

Results
Median SUV\(_{mean}\) in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUV\(_{max}\) in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found.

Conclusions
In patients with solid tumors imaged with [\(^{68}\)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.
KW  - CXCR4
KW  - C-X-C motif chemokine receptor 4
KW  - PET
KW  - [68Ga]PentixaFor
KW  - [177Lu]/[90Y]PentixaTher
KW  - theranostics
KW  - endoradiotherapy
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324622
VL  - 24
IS  - 4
ER  - 
TY  - JOUR
A1  - Werner, Rudolf
A1  - Hänscheid, Heribert
A1  - Leal, Jeffrey P.
A1  - Javadi, Mehrbod S.
A1  - Higuchi, Takahiro
A1  - Lodge, Martin A.
A1  - Buck, Andreas K.
A1  - Pomper, Martin G.
A1  - Lapa, Constantin
A1  - Rowe, Steven P.
T1  - Impact of Tumor Burden on Quantitative [\(^{68}\)Ga]DOTATOC Biodistribution
JF  - Molecular Imaging and Biology
N2  - Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([\(^{68}\)Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [\(^{68}\)Ga]DOTATATE, we aimed to quantitatively investigate the biodistribution of [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([68Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden.
Procedures: Of the 44 included patients, 36/44 (82%) patients demonstrated suspicious radiotracer uptake on [\(^{68}\)Ga]DOTATOC positron emission tomography (PET)/x-ray computed tomography (CT). Volumes of Interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUV\(_{mean}\)) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUV\(_{mean}\), maximum standardized uptake value (SUV\(_{max}\)), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman’s rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden. 
Results: The median SUV\(_{mean}\) was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUV\(_{mean}\) 6.9, SUV\(_{max}\) 35.5, TBM 42.6g, and TBU 1.2%. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUV\(_{mean}\) increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUV\(_{mean}\) nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3%) vs. higher TBU (>7%), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET. 
Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [\(^{68}\)Ga]DOTATOC PET/CT. Potential implications include increased normal organ dose with [\(^{177}\)Lu-DOTA]\(^0\)-D-Phe\(^1\)-Tyr\(^3\)-Octreotide and decreased absolute lesion detection with [\(^{68}\)Ga]DOTATOC in high NET burden.
KW  - somatostatin receptor
KW  - Positronen-Emissions-Tomografie
KW  - quantification
KW  - [68Ga]DOTATOC
KW  - neuroendocrine tumor
KW  - SSTR-PET
KW  - theranostics
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170280
ER  - 
TY  - JOUR
A1  - Matsusaka, Yohji
A1  - Chen, Xinyu
A1  - Arias-Loza, Paula
A1  - Werner, Rudolf A.
A1  - Nose, Naoko
A1  - Sasaki, Takanori
A1  - Rowe, Steven P.
A1  - Pomper, Martin G.
A1  - Lapa, Constantin
A1  - Higuchi, Takahiro
T1  - In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [\(^{18}\)F]Me4FDG PET in Rats
JF  - Molecular Imaging
N2  - Background. Mediating glucose absorption in the small intestine and renal clearance, sodium glucose cotransporters (SGLTs) have emerged as an attractive therapeutic target in diabetic patients. A substantial fraction of patients, however, only achieve inadequate glycemic control. Thus, we aimed to assess the potential of the SGLT-targeting PET radiotracer alpha-methyl-4-deoxy-4-[\(^{18}\)F]fluoro-D-glucopyranoside ([\(^{18}\)F]Me4FDG) as a noninvasive intestinal and renal biomarker of SGLT-mediated glucose transport. Methods. We investigated healthy rats using a dedicated small animal PET system. Dynamic imaging was conducted after administration of the reference radiotracer 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose ([\(^{18}\)F]FDG), or the SGLT-targeting agent, [\(^{18}\)F]Me4FDG either directly into the digestive tract (for assessing intestinal absorption) or via the tail vein (for evaluating kidney excretion). To confirm the specificity of [18F]Me4FDG and responsiveness to treatment, a subset of animals was also pretreated with the SGLT inhibitor phlorizin. In this regard, an intraintestinal route of administration was used to assess tracer absorption in the digestive tract, while for renal assessment, phlorizin was injected intravenously (IV). Results. Serving as reference, intestinal administration of [\(^{18}\)F]FDG led to slow absorption with retention of % of administered radioactivity at 15 min. [\(^{18}\)F]Me4FDG, however, was rapidly absorbed into the blood and cleared from the intestine within 15 min, leading to markedly lower tracer retention of % (). Intraintestinal phlorizin led to marked increase of [\(^{18}\)F]Me4FDG uptake (15 min, %; vs. untreated controls), supporting the notion that this PET agent can measure adequate SGLT inhibition in the digestive tract. In the kidneys, radiotracer was also sensitive to SGLT inhibition. After IV injection, [\(^{18}\)F]Me4FDG reabsorption in the renal cortex was significantly suppressed by phlorizin when compared to untreated animals (%ID/g at 60 min, vs. untreated controls, ; ). Conclusion. As a noninvasive read-out of the concurrent SGLT expression in both the digestive tract and the renal cortex, [\(^{18}\)F]Me4FDG PET may serve as a surrogate marker for treatment response to SGLT inhibition. As such, [\(^{18}\)F]Me4FDG may enable improvement in glycemic control in diabetes by PET-based monitoring strategies.
KW  - Sodium-Glucose Cotransporters (SGLTs)
KW  - diabetes
KW  - rats
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300708
VL  - 2022
ER  - 
TY  - JOUR
A1  - Philipp-Abbrederis, Kathrin
A1  - Herrmann, Ken
A1  - Knop, Stefan
A1  - Schottelius, Margret
A1  - Eiber, Matthias
A1  - Lückerath, Katharina
A1  - Pietschmann, Elke
A1  - Habringer, Stefan
A1  - Gerngroß, Carlos
A1  - Franke, Katharina
A1  - Rudelius, Martina
A1  - Schirbel, Andreas
A1  - Lapa, Constantin
A1  - Schwamborn, Kristina
A1  - Steidle, Sabine
A1  - Hartmann, Elena
A1  - Rosenwald, Andreas
A1  - Kropf, Saskia
A1  - Beer, Ambros J
A1  - Peschel, Christian
A1  - Einsele, Hermann
A1  - Buck, Andreas K
A1  - Schwaiger, Markus
A1  - Götze, Katharina
A1  - Wester, Hans-Jürgen
A1  - Keller, Ulrich
T1  - In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma
JF  - EMBO Molecular Medicine
N2  - CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.
KW  - FDG PET/CT
KW  - cells
KW  - CXCR4/SDF-1
KW  - CXCR4
KW  - multiple myeloma
KW  - positron emission tomography
KW  - chemokine receptor
KW  - in vivo imaging
KW  - malignancies
KW  - involvement
KW  - microenvironment
KW  - survival
KW  - cancer
KW  - autologous transplantation
KW  - bone disease
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148738
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Lapa, Constantin
A1  - Bluemel, Christina
A1  - Lückerath, Katharina
A1  - Schirbel, Andreas
A1  - Strate, Alexander
A1  - Buck, Andreas K.
A1  - Herrmann, Ken
T1  - Influence of the amount of co-infused amino acids on post-therapeutic potassium levels in peptide receptor radionuclide therapy
N2  - Background

Peptide receptor radionuclide therapy (PRRT) is routinely used for advanced or metastasized neuroendocrine tumours (NET). To prevent nephrotoxicity, positively charged amino acids (AA) are co-infused. The aim of this study was to correlate the risk for therapy-related hyperkalaemia with the total amount of AA infused.

Methods

Twenty-two patients undergoing PRRT with standard activities of 177Lu-DOTATATE/-TOC were monitored during two following treatment cycles with co-infusion of 75 and 50 g of AA (L-arginine and L-lysine), respectively. Mean serum levels of potassium and other parameters (glomerular filtration rate [GFR], creatinine, blood urea nitrogen [BUN], phosphate, chloride, lactate dehydrogenase) prior to, 4 h and 24 h after AA infusion were compared.

Results

Self-limiting hyperkalaemia (>5.0 mmol/l) resolving after 24 h occurred in 91% (20/22) of patients in both protocols. Potassium levels, BUN, creatinine, GFR, phosphate, chloride and LDH showed a similar range at 4 h after co-infusion of 75 or 50 g of AA, respectively (p > 0.05). Only GFR and creatinine levels at 24 h varied significantly between the two co-infusion protocols (p < 0.05).

Conclusions

Hyperkalaemia is a frequent side effect of AA infusion in PRRT. Varying the dose of co-infused amino acids did not impact on the incidence and severity of hyperkalaemia.
KW  - NET
KW  - PRRT
KW  - Hyperkalaemia
KW  - Arginine
KW  - Lysine
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110617
ER  - 
TY  - INPR
A1  - Werner, Rudolf A.
A1  - Bundschuh, Ralph A.
A1  - Bundschuh, Lena
A1  - Javadi, Mehrbod S.
A1  - Leal, Jeffrey P.
A1  - Higuchi, Takahiro
A1  - Pienta, Kenneth J.
A1  - Buck, Andreas K.
A1  - Pomper, Martin G.
A1  - Gorin, Michael A.
A1  - Lapa, Constantin
A1  - Rowe, Steven P.
T1  - Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging
T2  - Journal of Nuclear Medicine
N2  - Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center. 
Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed.
Results: The number of target lesions identified by each observer were as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least two individual observers (all four readers selected the same target lesion in 58/125 (46.4%) instances, three readers in 40/125 (32%) and two observers in 27/125 (21.6%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC=0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC=0.84), with a significant difference for ER (ICC=0.97) vs. IR (ICC=0.74, P=0.005).
Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.
KW  - 18F-DCFPyL
KW  - Positronen-Emissions-Tomografie
KW  - PSMA-RADS
KW  - interreader
KW  - interobserver
KW  - PSMA
KW  - prostate cancer
KW  - RADS
KW  - reporting and data system
KW  - PET
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167788
SN  - 0161-5505
N1  - This research was originally published in JNM. Rudolf A. Werner, Ralph A. Bundschuh, Lena Bundschuh, Mehrbod S. Javadi, Jeffrey P. Leal, Takahiro Higuchi, Kenneth J. Pienta, Andreas K. Buck, Martin G. Pomper, Michael A. Gorin, Constantin Lapa and Steven P. Rowe. Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on 18F-DCFPyL PET/CT Imaging. J Nucl Med 2018;59:1857-1864 © SNMMI.
ER  - 
TY  - CHAP
A1  - Werner, Rudolf
A1  - Chen, Xinyu
A1  - Lapa, Constantin
A1  - Robinson, Simon
A1  - Higuchi, Takahiro
T1  - Intracellular behavior of the novel sympathetic nerve agent \(^{18}\)F-LMI1195
T2  - Journal of Nuclear Cardiology
N2  - No abstract available.
KW  - Herz
KW  - PET
KW  - sympathetic nerve
KW  - autonomic nervous system
KW  - 18F-LMI1195
KW  - positron emission tomography
KW  - heart
KW  - cardiac
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161137
SN  - 1071-3581
N1  - This is a post-peer-review, pre-copyedit version of an article published in J Nucl Cardiol. ISSN: 1071-3581. Supplement (2017) Aug;24;4: 1461-1496. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12350-017-0984-y
VL  - 24
IS  - 4 Supplement (2017) Aug
ER  - 
TY  - JOUR
A1  - Hänscheid, Heribert
A1  - Hartrampf, Philipp E.
A1  - Schirbel, Andreas
A1  - Buck, Andreas K.
A1  - Lapa, Constantin
T1  - Intraindividual comparison of [\(^{177}\)Lu]Lu-DOTA-EB-TATE and [\(^{177}\)Lu]Lu-DOTA-TOC
JF  - European Journal of Nuclear Medicine and Molecular Imaging
N2  - Purpose
The radiolabelled somatostatin analogue [\(^{177}\)Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [\(^{177}\)Lu]Lu-DOTA-TOC.
Methods
Activity kinetics in organs and tumours after [\(^{177}\)Lu]Lu-DOTA-EB-TATE and [\(^{177}\)Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy.
Resuluts
In comparison to [\(^{177}\)Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [\(^{177}\)Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [\(^{177}\)Lu]Lu-DOTA-TOC in 4 of 5 patients.
Conclusions
Prior to a treatment with [\(^{177}\)Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances.
KW  - intraindividual comparison
KW  - DOTA-EB-TATE
KW  - somatostatin receptor
KW  - evans blue
KW  - biokinetics
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265470
SN  - 1619-7089
VL  - 48
IS  - 8
ER  - 
TY  - JOUR
A1  - Rasche, Leo
A1  - Kumar, Manoj
A1  - Gershner, Grant
A1  - Samant, Rohan
A1  - Van Hemert, Rudy
A1  - Heidemeier, Anke
A1  - Lapa, Constantin
A1  - Bley, Thorsten
A1  - Buck, Andreas
A1  - McDonald, James
A1  - Hillengass, Jens
A1  - Epstein, Joshua
A1  - Thanendrarajan, Sharmilan
A1  - Schinke, Carolina
A1  - van Rhee, Frits
A1  - Zangari, Maurizio
A1  - Barlogie, Bart
A1  - Davies, Faith E.
A1  - Morgan, Gareth J.
A1  - Weinhold, Niels
T1  - Lack of Spleen Signal on Diffusion Weighted MRI is associated with High Tumor Burden and Poor Prognosis in Multiple Myeloma: A Link to Extramedullary Hematopoiesis?
JF  - Theranostics
N2  - Due to the low frequency of abnormalities affecting the spleen, this organ is often overlooked during radiological examinations. Here, we report on the unexpected finding, that the spleen signal on diffusion-weighted MRI (DW-MRI) is associated with clinical parameters in patients with plasma cell dyscrasias. Methods: We investigated the spleen signal on DW-MRI together with clinical and molecular parameters in 295 transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients and in 72 cases with monoclonal gammopathy of undetermined significance (MGUS). Results: Usually, the spleen is the abdominal organ with the highest intensities on DW-MRI. Yet, significant signal loss on DW-MRI images was seen in 71 of 295 (24%) NDMM patients. This phenomenon was associated with the level of bone marrow plasmacytosis (P=1x10(-10)) and International Staging System 3 (P=0.0001) but not with gain(1q), and del(17p) or plasma cell gene signatures. The signal was preserved in 72 individuals with monoclonal gammopathy of undetermined significance and generally re-appeared in MM patients responding to treatment, suggesting that lack of signal reflects increased tumor burden. While absence of spleen signal in MM patients with high risk disease defined a subgroup with very poor outcome, re-appearance of the spleen signal after autologous stem cell transplantation was seen in patients with improved outcome. Our preliminary observation suggests that extramedullary hematopoiesis in the spleen is a factor that modifies the DW-MRI signal of this organ. Conclusions: The DW-MRI spleen signal is a promising marker for tumor load and provides prognostic information in MM.
KW  - multiple myeloma
KW  - diffusion weighted mri
KW  - spleen
KW  - tumor burden
KW  - high risk
KW  - extramedullary hematopoiesis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224982
VL  - 9
IS  - 16
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Eissler, Christoph
A1  - Hayakawa, Nobuyuki
A1  - Arias-Loza, Paula
A1  - Wakabayashi, Hiroshi
A1  - Javadi, Mehrbod S.
A1  - Chen, Xinyu
A1  - Shinaji, Tetsuya
A1  - Lapa, Constantin
A1  - Pelzer, Theo
A1  - Higuchi, Takahiro
T1  - Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET
JF  - Scientific Reports
N2  - In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated \(^{18}\)F-fluorodeoxyglucose positron emission tomography (\(^{18}\)F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated \(^{18}\)F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n=6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, \(^{18}\)F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5±4.2 vs. 59.4±4.5%; HR: 331±35 vs. 309±24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1±0.8 vs. 10.2±1 Enddiastolic Volume/sec, P<0.01). Investigating a diabetic rat model, ECG-gated \(^{18}\)F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent.
KW  - diabetic cardiomyopathy
KW  - personalized treatment
KW  - precision medicine
KW  - ZDF rats
KW  - ECG
KW  - PET
KW  - \(^{18}\)F-fluorodeoxyglucose
KW  - \(^{18}\)F-FDG
KW  - diabetes
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171765
VL  - 8
IS  - 17631
ER  - 
TY  - CHAP
A1  - Werner, Rudolf
A1  - Lapa, Constantin
A1  - Buck, Andreas
A1  - Lassmann, Michael
A1  - Hänscheid, Heribert
T1  - Less is sometimes more – Accurate Dose Mapping after Endoradiotherapy with  \(^{177}\)Lu-DOTATATE/-TOC by One-Single Measurement after 96 h
T2  - Journal of Nuclear Medicine
N2  - No abstract available.
KW  - Neuroendocrine Tumor
KW  - theranostics
KW  - 177Lu-DOTATATE
KW  - 177Lu-DOTATOC
KW  - PRRT
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161168
UR  - http://jnm.snmjournals.org/content/58/supplement_1/247.abstract
SN  - 0161-5505
N1  - This research was originally published in JNM. Werner R.A., Lapa C., Buck A.K., Lassmann M., Hänscheid H.Less is sometimes more – Accurate Dose Mapping after Endoradiotherapy with 177Lu-DOTATATE/-TOC by One-Single Measurement after 96 h. J Nucl Med May 1, 2017 vol. 58 no. supplement 1:247. © SNMMI
VL  - 58
IS  - No. Supplement 1
PB  - Society of Nuclear Medicine and Molecular Imaging
ER  - 
TY  - JOUR
A1  - Werner, Rudolf
A1  - Wakabayashi, Hiroshi
A1  - Bauer, Jochen
A1  - Schütz, Claudia
A1  - Zechmeister, Christina
A1  - Hayakawa, Nobuyuki
A1  - Javadi, Mehrbod S.
A1  - Lapa, Constantin
A1  - Jahns, Roland
A1  - Ergün, Süleyman
A1  - Jahns, Valerie
A1  - Higuchi, Takahiro
T1  - Longitudinal \(^{18}\)F-FDG PET imaging in a Rat Model of Autoimmune Myocarditis
JF  - European Heart Journal Cardiovascular Imaging
N2  - Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis.

Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund’s adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo \(^{18}\)F-FDG PET signalling (R\(^2\) = 0.92) as well as with ex vivo 18F-FDG autoradiography (R\(^2\) = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at \(^{18}\)F-FDG decrease).

Conclusion: \(^{18}\)F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.
KW  - positron emission tomography
KW  - Myokarditis
KW  - myocarditis
KW  - inflammation
KW  - 18F-FDG
KW  - PET
KW  - personalized treatment
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165601
SN  - 2047-2404
ER  - 
TY  - INPR
A1  - Nose, Naoko
A1  - Werner, Rudolf A.
A1  - Ueda, Yuichiro
A1  - Günther, Katharina
A1  - Lapa, Constantin
A1  - Javadi, Mehrbod S.
A1  - Fukushima, Kazuhito
A1  - Edenhofer, Frank
A1  - Higuchi, Takahiro
T1  - Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay
T2  - International Journal of Cardiology
N2  - Background: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. Material and Methods: Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F-2-fluoro-2-deoxy-D-glucose (\(^{18}\)F-FDG) and \(^{125}\)I-β-methyl-iodophenyl-pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively. Results: After cardiac differentiation of hiPSC, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM. Conclusions: During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.
KW  - tracer
KW  - Stammzelle
KW  - induced pluripotent stem cells
KW  - cardiomyocytes
KW  - fatty acid
KW  - stem cell therapy
KW  - hiPSC-CM
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-163320
SN  - 0167-5273
ER  - 
TY  - JOUR
A1  - Nose, Naoko
A1  - Werner, Rudolf A.
A1  - Ueda, Yuichiro
A1  - Günther, Katharina
A1  - Lapa, Constantin
A1  - Javadi, Mehrbod S.
A1  - Fukushima, Kazuhito
A1  - Edenhofer, Frank
A1  - Higuchi, Takahiro
T1  - Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay
JF  - International Journal of Cardiology
N2  - BACKGROUND:
Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay.

MATERIAL AND METHODS:
Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F‑2‑fluoro‑2‑deoxy‑d‑glucose (\(^{18}\)F-FDG) and \(^{125}\)I‑β‑methyl‑iodophenyl‑pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively.

RESULTS:
After cardiac differentiation of hiPSCs, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM.

CONCLUSIONS:
During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.
KW  - tracer
KW  - Stammzelle
KW  - induced pluripotent stem cells
KW  - cardiomyocytes
KW  - fatty acid
KW  - stem cell therapy
KW  - hiPSC-CM
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170699
VL  - 269
ER  - 
TY  - JOUR
A1  - Hartrampf, Philipp E.
A1  - Heinrich, Marieke
A1  - Seitz, Anna Katharina
A1  - Brumberg, Joachim
A1  - Sokolakis, Ioannis
A1  - Kalogirou, Charis
A1  - Schirbel, Andreas
A1  - Kübler, Hubert
A1  - Buck, Andreas K.
A1  - Lapa, Constantin
A1  - Krebs, Markus
T1  - Metabolic Tumour Volume from PSMA PET/CT Scans of Prostate Cancer Patients during Chemotherapy — Do Different Software Solutions Deliver Comparable Results?
JF  - Journal of Clinical Medicine
N2  - (1) Background: Prostate-specific membrane antigen (PSMA)-derived tumour volume (PSMA-TV) and total lesion PSMA (TL-PSMA) from PSMA PET/CT scans are promising biomarkers for assessing treatment response in prostate cancer (PCa). Currently, it is unclear whether different software tools for assessing PSMA-TV and TL-PSMA produce comparable results. (2) Methods: \(^{68}\)Ga-PSMA PET/CT scans from n = 21 patients with castration-resistant PCa (CRPC) receiving chemotherapy were identified from our single-centre database. PSMA-TV and TL-PSMA were calculated with Syngo.via (Siemens) as well as the freely available Beth Israel plugin for FIJI (Fiji Is Just ImageJ) before and after chemotherapy. While statistical comparability was illustrated and quantified via Bland-Altman diagrams, the clinical agreement was estimated by matching PSMA-TV, TL-PSMA and relative changes of both variables during chemotherapy with changes in serum PSA (ΔPSA) and PERCIST (Positron Emission Response Criteria in Solid Tumors). (3) Results: Comparing absolute PSMA-TV and TL-PSMA as well as Bland–Altman plotting revealed a good statistical comparability of both software algorithms. For clinical agreement, classifying therapy response did not differ between PSMA-TV and TL-PSMA for both software solutions and showed highly positive correlations with BR. (4) Conclusions: due to the high levels of statistical and clinical agreement in our CRPC patient cohort undergoing taxane chemotherapy, comparing PSMA-TV and TL-PSMA determined by Syngo.via and FIJI appears feasible.
KW  - prostate-specific membrane antigen (PSMA)
KW  - metabolic tumour volume (MTV)
KW  - total lesion PSMA
KW  - biomarker
KW  - software
KW  - comparability
KW  - agreement
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205893
SN  - 2077-0383
VL  - 9
IS  - 5
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Bundschuh, Ralph A.
A1  - Bundschuh, Lena
A1  - Javadi, Mehrbod S.
A1  - Higuchi, Takahiro
A1  - Weich, Alexander
A1  - Sheikhbahaei, Sara
A1  - Pienta, Kenneth J.
A1  - Buck, Andreas K.
A1  - Pomper, Martin G.
A1  - Gorin, Michael A.
A1  - Lapa, Constantin
A1  - Rowe, Steven P.
T1  - MI-RADS: Molecular Imaging Reporting and Data Systems – A Generalizable Framework for Targeted Radiotracers with Theranostic Implications
JF  - Annals of Nuclear Medicine
N2  - Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET) imaging agents for staging and restaging of prostate carcinoma or neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Both framework systems may contribute to increase the level of a reader’s confidence and to navigate the imaging interpreter through indeterminate lesions, so that appropriate workup for equivocal findings can be pursued. Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e. if the reader is familiar with one system, the other system can readily be applied as well. In the present review we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a future role of the umbrella framework MI-RADS compared to other harmonization systems.
KW  - PET
KW  - Positronen-Emissions-Tomografie
KW  - prostate cancer
KW  - neuroendocrine tumor
KW  - prostate-specific membrane antigen (PSMA)
KW  - somatostatin receptor (SSTR)
KW  - positron emission tomography
KW  - theranostics
KW  - standardization
KW  - RADS
KW  - reporting and data systems
KW  - personalized medicine
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166995
SN  - 0914-7187
ER  - 
TY  - JOUR
A1  - Chen, Xinyu
A1  - Werner, Rudolf A.
A1  - Koshino, Kazuhiro
A1  - Nose, Naoko
A1  - Mühlig, Saskia
A1  - Rowe, Steven P.
A1  - Pomper, Martin G.
A1  - Lapa, Constantin
A1  - Decker, Michael
A1  - Higuchi, Takahiro
T1  - Molecular Imaging-Derived Biomarker of Cardiac Nerve Integrity - Introducing High NET Affinity PET Probe \(^{18}\)F-AF78
JF  - Theranostics
N2  - Background: Radiolabeled agents that are substrates for the norepinephrine transporter (NET) can be used to quantify cardiac sympathetic nervous conditions and have been demonstrated to identify high-risk congestive heart failure (HF) patients prone to arrhythmic events. We aimed to fully characterize the kinetic profile of the novel \(^{18}\)F-labeled NET probe AF78 for PET imaging of the cardiac sympathetic nervous system (SNS) among various species.

Methods: \(^{18}\)F-AF78 was compared to norepinephrine (NE) and established SNS radiotracers by employing in vitro cell assays, followed by an in vivo PET imaging approach with healthy rats, rabbits and nonhuman primates (NHPs). Additionally, chase protocols were performed in NHPs with NET inhibitor desipramine (DMI) and the NE releasing stimulator tyramine (TYR) to investigate retention kinetics in cardiac SNS.

Results: Relative to other SNS radiotracers, 18F-AF78 showed higher transport affinity via NET in a cell-based competitive uptake assay (IC\(^{50}\) 0.42 ± 0.14 µM), almost identical to that of NE (IC\(^{50}\), 0.50 ± 0.16 µM, n.s.). In rabbits and NHPs, initial cardiac uptake was significantly reduced by NET inhibition. Furthermore, cardiac tracer retention was not affected by a DMI chase protocol but was markedly reduced by intermittent TYR chase, thereby suggesting that \(^{18}\)F-AF78 is stored and can be released via the synaptic vesicular turnover process. Computational modeling hypothesized the formation of a T-shaped π-π stacking at the binding site, suggesting a rationale for the high affinity of \(^{18}\)F-AF78.

Conclusion: \(^{18}\)F-AF78 demonstrated high in vitro NET affinity and advantageous in vivo radiotracer kinetics across various species, indicating that \(^{18}\)F-AF78 is an SNS imaging agent with strong potential to guide specific interventions in cardiovascular medicine.
KW  - norepinephrine transporter
KW  - T-shaped π-π stacking
KW  - nonhuman primates
KW  - radiotracer kinetics
KW  - cardiac innervation imaging
KW  - sympathetic nervous system
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300685
VL  - 12
IS  - 9
SP  - 4446
EP  - 4458
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Chen, Xinyu
A1  - Rowe, Steven P.
A1  - Lapa, Constantin
A1  - Javadi, Mehrbod S.
A1  - Higuchi, Takahiro
T1  - Moving into the Next Era of PET Myocardial Perfusion Imaging - Introduction of Novel \(^{18}\)F-labeled Tracers
JF  - The International Journal of Cardiovascular Imaging
N2  - The heart failure (HF) epidemic continues to rise with coronary artery disease (CAD) as one of its main causes. Novel concepts for risk stratification to guide the referring cardiologist towards revascularization procedures are of significant value. Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) agents has demonstrated high accuracy for the detection of clinically relevant stenoses. With positron emission tomography (PET) becoming more widely available, mainly due to its diagnostic performance in oncology, perfusion imaging with that modality is more practical than in the past and overcomes existing limitations of SPECT MPI. Advantages of PET include more reliable quantification of absolute myocardial blood flow, the routine use of computed tomography for attenuation correction, a higher spatiotemporal resolution and a higher count sensitivity. Current PET radiotracers such as rubidium-82 (half-life, 76 sec), oxygen-15 water (2 min) or nitrogen-13 ammonia (10 min) are labeled with radionuclides with very short half-lives, necessitating that stress imaging is performed under pharmacological vasodilator stress instead of exercise testing. However, with the introduction of novel 18F-labeled MPI PET radiotracers (half-life, 110 min), the intrinsic advantages of PET can be combined with exercise testing. Additional advantages of those radiotracers include, but are not limited to: potentially improved cost-effectiveness due to the use of pre-existing delivery systems and superior imaging qualities, mainly due to the shortest positron range among available PET MPI probes. In the present review, widely used PET MPI radiotracers will be reviewed and potential novel 18F-labeled perfusion radiotracers will be discussed.
KW  - heart failure with mid-range ejection fraction
KW  - Positronenemissionstomografie
KW  - coronary artery disease
KW  - precision medicine
KW  - positron emission tomography
KW  - PET
KW  - SPECT
KW  - myocardial perfusion imaging
KW  - MPI
KW  - 18F-flurpiridaz
KW  - 18FFBnTP
KW  - HFmrEF
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169134
SN  - 1569-5794
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Ordonez, Alvaro A.
A1  - Sanchez-Bautista, Julian
A1  - Marcus, Charles
A1  - Lapa, Constantin
A1  - Rowe, Steven P.
A1  - Pomper, Martin G.
A1  - Leal, Jeffrey P.
A1  - Lodge, Martin A.
A1  - Javadi, Mehrbod S.
A1  - Jain, Sanjay K.
A1  - Higuchi, Takahiro
T1  - Novel functional renal PET imaging with 18F-FDS in human subjects
JF  - Clinical Nuclear Medicine
N2  - The novel PET probe 2-deoxy-2-18F-fluoro-D-sorbitol (18F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in two human volunteers. 18F-FDS was produced by a simple one-step reduction from 18F-FDG. On dynamic renal PET, the cortex was delineated and activity gradually transited in the parenchyma, followed by radiotracer excretion. No adverse effects were reported. Given the higher spatiotemporal resolution of PET relative to conventional scintigraphy, 18F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from 18F-FDG, 18F-FDS is virtually available at any PET facility with radiochemistry infrastructure.
KW  - 2-deoxy-2-18F-fluoro-D-sorbitol
KW  - Positronen-Emissions-Tomografie
KW  - 18F-FDS
KW  - renal imaging
KW  - Positron-Emission Tomography
KW  - split renal function
KW  - kidney
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174634
SN  - 0363-9762
VL  - 44
IS  - 5
ER  - 
TY  - INPR
A1  - Werner, Rudolf A.
A1  - Bundschuh, Ralph A.
A1  - Bundschuh, Lena
A1  - Fanti, Stefano
A1  - Javadi, Mehrbod S.
A1  - Higuchi, Takahiro
A1  - Weich, A.
A1  - Pienta, Kenneth J.
A1  - Buck, Andreas K.
A1  - Pomper, Martin G.
A1  - Gorin, Michael A.
A1  - Herrmann, Ken
A1  - Lapa, Constantin
A1  - Rowe, Steven P.
T1  - Novel Structured Reporting Systems for Theranostic Radiotracers
T2  - Journal of Nuclear Medicine
N2  - Standardized reporting is more and more routinely implemented in clinical practice and such structured reports have a major impact on a large variety of medical fields, e.g. laboratory medicine, pathology, and, recently, radiology. Notably, the field of nuclear medicine is constantly evolving, as novel radiotracers for numerous clinical applications are developed. Thus, framework systems for standardized reporting in this field may a) increase clinical acceptance of new radiotracers, b) allow for inter- and intra-center comparisons for quality assurance, and c) may be used in (global) multi-center studies to ensure comparable results and enable efficient data abstraction. In the last two years, several standardized framework systems for positron emission tomography (PET) radiotracers with potential theranostic applications have been proposed. These include systems for prostate-specific membrane antigen (PSMA)-targeted PET agents for the diagnosis and treatment of prostate cancer (PCa) and somatostatin receptor (SSTR)-targeted PET agents for the diagnosis and treatment of neuroendocrine neoplasias. In the present review, those standardized framework systems for PSMA- and SSTR-targeted PET will be briefly introduced followed by an overview of their advantages and limitations. In addition, potential applications will be defined, approaches to validate such concepts will be proposed, and future perspectives will be discussed.
KW  - standardized reporting
KW  - Positronen-Emissions-Tomografie
KW  - prostate cancer
KW  - neuroendocrine neoplasia
KW  - 68Ga-DOTATATE
KW  - 68Ga-DOTATOC
KW  - 68Ga-DOTANOC
KW  - somatostatin receptor
KW  - SSTR
KW  - prostate-specific membrane antigen
KW  - PSMA
KW  - RADS
KW  - PSMA-RADS
KW  - SSTR-RADS
KW  - MI-RADS
KW  - PROMISE
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174629
SN  - 0161-5505
N1  - This research was originally published in JNM. Authors: Rudolf A. Werner, Ralph A. Bundschuh, Lena Bundschuh, Stefano Fanti, Mehrbod S. Javadi, Takahiro Higuchi, A. Weich, Kenneth J. Pienta, Andreas K. Buck, Martin G. Pomper, Michael A. Gorin, Ken Herrmann, Constantin Lapa, Steven P. Rowe. Novel Structured Reporting Systems for Theranostic Radiotracers. J Nucl Med May 1, 2019 vol. 60 no. 5 577-584 © SNMMI.
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Sheikhbahaei, Sara
A1  - Jones, Krystyna M.
A1  - Javadi, Mehrbod S.
A1  - Solnes, Lilja B.
A1  - Ross, Ashley E.
A1  - Allaf, Mohamad E.
A1  - Pienta, Kenneth J.
A1  - Lapa, Constantin
A1  - Buck, Andreas K.
A1  - Higuchi, Takahiro
A1  - Pomper, Martin G.
A1  - Gorin, Micheal A.
A1  - Rowe, Steven P.
T1  - Patterns of uptake of prostate-specific membrane antigen (PSMA)-targeted \(^{18}\)F-DCFPyL in peripheral ganglia
JF  - Annals of Nuclear Medicine
N2  - Objective: Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent \(^{18}\)F-DCFPyL. 
Methods: A total of 98 patients who underwent \(^{18}\)F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUV\(_{max}\)), and maximum standardized uptake value corrected to lean body mass (SUL\(_{max}\)) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUV\(_{max}\) and SUL\(_{max}\) values by the mean uptake in the ascending aorta (Aortamean) and the right gluteus muscle (Gluteusmean). 
Results: Overall, 95 of 98 (96.9%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4%), followed by the cervical ganglia (51/76, 67.1%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80%) and cervical 30/51 (58.8%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8%) of the analyzed stellate ganglia and in 45/76 (59.2%) of the celiac ganglia, whereas only 5/76 (6.6%) of the sacral ganglia demonstrated \(^{18}\)F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9%) and cervical ganglia (19/ 22, 86.4%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts. 
Conclusion: As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients’ cancers must be understood. This is the first systematic evaluation of the uptake of \(^{18}\)F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research.
KW  - 18F-DCFPL
KW  - Positronen-Emissions-Tomografie
KW  - Prostata
KW  - PSMA
KW  - Ganglia
KW  - Pitfall
KW  - PET
KW  - Tracer
KW  - Radiotracer
KW  - Imaging pitfalls
KW  - Prostate Cancer
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166971
SN  - 0914-7187
VL  - 31
IS  - 9
ER  - 
TY  - JOUR
A1  - Lapa, Constantin
A1  - Kircher, Malte
A1  - Hänscheid, Heribert
A1  - Schirbel, Andreas
A1  - Grigoleit, Götz Ulrich
A1  - Klinker, Erdwine
A1  - Böck, Markus
A1  - Samnick, Samuel
A1  - Pelzer, Theo
A1  - Buck, Andreas K
T1  - Peptide receptor radionuclide therapy as a new tool in treatment-refractory sarcoidosis - initial experience in two patients
JF  - Theranostics
N2  - Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that can involve virtually all organ systems. Whereas most patients present without symptoms, progressive and disabling organ failure can occur in up to 10% of subjects. Somatostatin receptor (SSTR)-directed peptide receptor radionuclide therapy (PRRT) has recently received market authorization for treatment of SSTR-positive neuroendocrine tumors.

Methods: 
We describe the first case series comprising two patients with refractory multi-organ involvement of sarcoidosis who received 4 cycles of PRRT.

Results: 
PRRT was well-tolerated without any acute adverse effects. No relevant toxicities could be recorded during follow-up. Therapy resulted in partial response accompanied by a pronounced reduction in pain (patient #1) and stable disease regarding morphology as well as disease activity (patient #2), respectively.

Conclusion: 
Peptide receptor radionuclide therapy in sarcoidosis is feasible and might be a new valuable tool in patients with otherwise treatment-refractory disease. Given the long experience with and good tolerability of PRRT, further evaluation of this new treatment option for otherwise treatment-refractory sarcoidosis in larger patient cohorts is warranted.
KW  - peptide receptor
KW  - PRRT
KW  - sarcoidosis
KW  - somatostatin receptors
KW  - radionuclide therapy
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158983
VL  - 8
IS  - 3
ER  - 
TY  - JOUR
A1  - Matsusaka, Yohji
A1  - Werner, Rudolf A.
A1  - Arias-Loza, Paula
A1  - Nose, Naoko
A1  - Sasaki, Takanori
A1  - Chen, Xinyu
A1  - Lapa, Constantin
A1  - Higuchi, Takahiro
T1  - Performance Evaluation of a Preclinical SPECT Scanner with a Collimator Designed for Medium-Sized Animals
JF  - Molecular Imaging
N2  - Background. Equipped with two stationary detectors, a large bore collimator for medium-sized animals has been recently introduced for dedicated preclinical single-photon emission computed tomography (SPECT) imaging. We aimed to evaluate the basic performance of the system using phantoms and healthy rabbits. Methods. A general-purpose medium-sized animal (GP-MSA) collimator with 135 mm bore diameter and thirty-three holes of 2.5 mm diameter was installed on an ultrahigh-resolution scanner equipped with two large stationary detectors (U-SPECT5-E/CT). The sensitivity and uniformity were investigated using a point source and a cylinder phantom containing 99mTc-pertechnetate, respectively. Uniformity (in %) was derived using volumes of interest (VOIs) on images of the cylinder phantom and calculated as , with lower values of % indicating superior performance. The spatial resolution and contrast-to-noise ratios (CNRs) were evaluated with images of a hot-rod Derenzo phantom using different activity concentrations. Feasibility of in vivo SPECT imaging was finally confirmed by rabbit imaging with the most commonly used clinical myocardial perfusion SPECT agent [99mTc]Tc-sestamibi (dynamic acquisition with a scan time of 5 min). Results. In the performance evaluation, a sensitivity of 790 cps/MBq, a spatial resolution with the hot-rod phantom of 2.5 mm, and a uniformity of 39.2% were achieved. The CNRs of the rod size 2.5 mm were 1.37, 1.24, 1.20, and 0.85 for activity concentration of 29.2, 1.0, 0.5, and 0.1 MBq/mL, respectively. Dynamic SPECT imaging in rabbits allowed to visualize most of the thorax and to generate time-activity curves of the left myocardial wall and ventricular cavity. Conclusion. Preclinical U-SPECT5-E/CT equipped with a large bore collimator demonstrated adequate sensitivity and resolution for in vivo rabbit imaging. Along with its unique features of SPECT molecular functional imaging is a superior collimator technology that is applicable to medium-sized animal models and thus may promote translational research for diagnostic purposes and development of novel therapeutics.
KW  - SPECT Scanner
KW  - medium-sized animals
KW  - performance
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300713
VL  - 2022
ER  - 
TY  - JOUR
A1  - Hoffmann, Jan V.
A1  - Janssen, Jan P.
A1  - Kanno, Takayuki
A1  - Shibutani, Takayuki
A1  - Onoguchi, Masahisa
A1  - Lapa, Constantin
A1  - Grunz, Jan-Peter
A1  - Buck, Andreas K.
A1  - Higuchi, Takahiro
T1  - Performance evaluation of fifth-generation ultra-high-resolution SPECT system with two stationary detectors and multi-pinhole imaging
JF  - EJNMMI Physics
N2  - Background 
Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT\(^+\)). 

Methods 
The new U-SPECT5-E with two stationary detectors was used for acquiring data with \(^{99m}\)Tc-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT\(^+\) for comparison. 

Results 
Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT\(^+\). In the visually analysed sections of the reconstructed mini Derenzo phantoms, rods as small as 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M) were resolved. Uniformity for maximum resolution recorded 40.7% (XUHR-M), 29.1% (GP-M, U-SPECT5-E), 16.3% (GP-M, U-SPECT\(^+\)) and 23.0% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60 to 1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR. 

Conclusions 
While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup.
KW  - small-animal imaging
KW  - SPECT
KW  - mouse
KW  - ollimator
KW  - post-reconstruction filtering
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230361
VL  - 7
ER  - 
TY  - INPR
A1  - Werner, Rudolf A.
A1  - Ilhan, Harun
A1  - Lehner, Sebastian
A1  - Papp, László
A1  - Zsótér, Norbert
A1  - Schatka, Imke
A1  - Muegge, Dirk O.
A1  - Javadi, Mehrbod S.
A1  - Higuchi, Takahiro
A1  - Buck, Andreas K.
A1  - Bartenstein, Peter
A1  - Bengel, Frank
A1  - Essler, Markus
A1  - Lapa, Constantin
A1  - Bundschuh, Ralph A.
T1  - Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy
T2  - Molecular Imaging and Biology
N2  - Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed.
Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters  (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated.
Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.).
Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
KW  - Pancreas
KW  - Positronen-Emissions-Tomografie
KW  - PET
KW  - neuroendocrine tumor
KW  - tumor heterogeneity
KW  - [68Ga]
KW  - [177Lu]-DOTATATE/-DOTATOC
KW  - PET/CT
KW  - SSTR
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164624
UR  - https://link.springer.com/article/10.1007/s11307-018-1252-5
SN  - 1536-1632
N1  - This is a post-peer-review, pre-copyedit version of an article published in Molecular Imaging and Biology. The final authenticated version is available online at: http://dx.doi.org/s11307-018-1252-5
N1  - Die finale Version dieses Artikels steht unter https://doi.org/10.1007/s11307-018-1252-5 bzw. http://nbn-resolving.org/urn:nbn:de:bvb:20-opus-167168 open access zur Verfügung.
ER  -