30503
2023
eng
2
15
article
1
--
2023-01-06
--
Predicting microenvironment in CXCR4- and FAP-positive solid tumors — a pan-cancer machine learning workflow for theranostic target structures
(1) Background: C-X-C Motif Chemokine Receptor 4 (CXCR4) and Fibroblast Activation Protein Alpha (FAP) are promising theranostic targets. However, it is unclear whether CXCR4 and FAP positivity mark distinct microenvironments, especially in solid tumors. (2) Methods: Using Random Forest (RF) analysis, we searched for entity-independent mRNA and microRNA signatures related to CXCR4 and FAP overexpression in our pan-cancer cohort from The Cancer Genome Atlas (TCGA) database — representing n = 9242 specimens from 29 tumor entities. CXCR4- and FAP-positive samples were assessed via StringDB cluster analysis, EnrichR, Metascape, and Gene Set Enrichment Analysis (GSEA). Findings were validated via correlation analyses in n = 1541 tumor samples. TIMER2.0 analyzed the association of CXCR4 / FAP expression and infiltration levels of immune-related cells. (3) Results: We identified entity-independent CXCR4 and FAP gene signatures representative for the majority of solid cancers. While CXCR4 positivity marked an immune-related microenvironment, FAP overexpression highlighted an angiogenesis-associated niche. TIMER2.0 analysis confirmed characteristic infiltration levels of CD8+ cells for CXCR4-positive tumors and endothelial cells for FAP-positive tumors. (4) Conclusions: CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets.
Cancers
2072-6694
10.3390/cancers15020392
urn:nbn:de:bvb:20-opus-305036
2023-03-14T06:04:09+00:00
sword
swordwue
attachment; filename=deposit.zip
ef321b506fda39e701eaba47282e1a54
Cancers (2023) 15:2, 392. https://doi.org/10.3390/cancers15020392
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
André Marquardt
Philipp Hartrampf
Philip Kollmannsberger
Antonio G. Solimando
Svenja Meierjohann
Hubert Kübler
Ralf Bargou
Bastian Schilling
Sebastian E. Serfling
Andreas Buck
Rudolf A. Werner
Constantin Lapa
Markus Krebs
eng
uncontrolled
machine learning
eng
uncontrolled
tumor microenvironment
eng
uncontrolled
immune infiltration
eng
uncontrolled
angiogenesis
eng
uncontrolled
mRNA
eng
uncontrolled
miRNA
eng
uncontrolled
transcriptome
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Urologische Klinik und Poliklinik
Pathologisches Institut
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Import
Center for Computational and Theoretical Biology
Comprehensive Cancer Center Mainfranken
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30503/cancers-15-00392-v3.pdf
30394
2023
eng
2
15
article
1
--
2023-02-17
--
Rationalizing the binding modes of PET radiotracers targeting the norepinephrine transporter
Purpose: A new PET radiotracer \(^{18}\)F-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure–activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. Methods: Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of \(^{18}\)F-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. Results: Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 µM, respectively), with meta-OH being the least active (22.67 µM). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer–NET interaction, whereby a T-shaped π–π stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. Conclusion: The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors.
Pharmaceutics
1999-4923
10.3390/pharmaceutics15020690
urn:nbn:de:bvb:20-opus-303949
2023-03-14T05:52:25+00:00
sword
swordwue
attachment; filename=deposit.zip
0163457f22e9ed16b9172737a681a8f1
Pharmaceutics (2023) 15:2, 690. https://doi.org/10.3390/pharmaceutics15020690
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Anna Tutov
Xinyu Chen
Rudolf A. Werner
Saskia Mühlig
Thomas Zimmermann
Naoko Nose
Kazuhiro Koshino
Constantin Lapa
Michael Decker
Takahiro Higuchi
eng
uncontrolled
positron emission tomography
eng
uncontrolled
norepinephrine transporter
eng
uncontrolled
sympathetic nervous system
eng
uncontrolled
structure–activity relationships
eng
uncontrolled
T-shaped π–π stacking
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Institut für Pharmazie und Lebensmittelchemie
Import
Deutsches Zentrum für Herzinsuffizienz (DZHI)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30394/pharmaceutics-15-00690.pdf
32443
2023
eng
1833-1834
6
50
article
1
--
--
--
Successful combination of selpercatinib and radioiodine after pretherapeutic dose estimation in RET-altered thyroid carcinoma
No abstract available.
European Journal of Nuclear Medicine and Molecular Imaging
10.1007/s00259-022-06061-8
urn:nbn:de:bvb:20-opus-324435
@articleWerner.2023, author = Werner, Rudolf A. and Sayehli, Cyrus and Hänscheid, Heribert and Higuchi, Takahiro and Serfling, Sebastian E. and Fassnacht, Martin and Goebeler, Maria-Elisabeth and Buck, Andreas K. and Kroiss, Matthias, year = 2023, title = Successful combination of selpercatinib and radioiodine after pretherapeutic dose estimation in RET-altered thyroid carcinoma, pages = 1833–1834, volume = 50, number = 6, journal = European journal of nuclear medicine and molecular imaging, doi = 10.1007/s00259-022-06061-8
md5:7f5760f89c1db2356956d4f62a5db3cb
2023-08-12T10:19:33+00:00
/tmp/phpUZfgtd
bibtex
64d75cb5648f78.75399079
European Journal of Nuclear Medicine and Molecular Imaging (2023) 50:6, 1833-1834 DOI: 10.1007/s00259-022-06061-8
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Cyrus Sayehli
Heribert Hänscheid
Takahiro Higuchi
Sebastian E. Serfling
Martin Fassnacht
Maria-Elisabeth Goebeler
Andreas K. Buck
Matthias Kroiss
eng
uncontrolled
papillary thyroid carcinoma (PTC)
eng
uncontrolled
selpercatinib
eng
uncontrolled
radioiodine
eng
uncontrolled
combination
eng
uncontrolled
thyroid carcinoma (TC)
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/32443/s00259-022-06061-8.pdf
32460
2023
eng
662-664
2
30
article
1
--
--
--
Unfolding the cardioprotective potential of sigma-1 receptor-directed molecular imaging
No abstract available.
Journal of Nuclear Cardiology
10.1007/s12350-022-03077-3
urn:nbn:de:bvb:20-opus-324600
@articleHiguchi.2023, author = Higuchi, Takahiro and Werner, Rudolf A., year = 2023, title = Unfolding the cardioprotective potential of sigma-1 receptor-directed molecular imaging, pages = 662–664, volume = 30, number = 2, journal = Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, doi = 10.1007/s12350-022-03077-3
md5:e2cbf4e0d90217433b5bd2d0453bdd90
2023-08-12T10:37:25+00:00
/tmp/phpKtPjJc
bibtex
64d760e520e2f0.54800151
Journal of Nuclear Cardiology (2023) 30:2, 662-664. DOI: 10.1007/s12350-022-03077-3
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Takahiro Higuchi
Rudolf A. Werner
eng
uncontrolled
Journal of Nuclear Cardiology
eng
uncontrolled
editorial
eng
uncontrolled
sigma-1 receptor-directed molecular imaging
eng
uncontrolled
cardioprotective potential
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Deutsches Zentrum für Herzinsuffizienz (DZHI)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/32460/s12350-022-03077-3.pdf
30070
2022
eng
2022
article
1
--
--
--
In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [\(^{18}\)F]Me4FDG PET in Rats
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.
Molecular Imaging
10.1155/2022/4635171
urn:nbn:de:bvb:20-opus-300708
@articleMatsusaka.2022, author = Matsusaka, Yohji and Chen, Xinyu and Arias-Loza, Paula and Werner, Rudolf A. and Nose, Naoko and Sasaki, Takanori and Rowe, Steven P. and Pomper, Martin G. and Lapa, Constantin and Higuchi, Takahiro, year = 2022, title = In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using 18FMe4FDG PET in Rats, pages = 4635171, volume = 2022, journal = Molecular imaging, doi = 10.1155/2022/4635171,
md5:d95edc215de887150d956e1ad1035fc1
2023-01-23T07:14:08+00:00
/tmp/phpIl8ujD
bibtex
63ce33c010fed2.40760513
Molecular Imaging 2022, Vol 2022, Article ID 4635171. DOI: 10.1155/2022/4635171
false
true
Yohji Matsusaka
Xinyu Chen
Paula Arias-Loza
Rudolf A. Werner
Naoko Nose
Takanori Sasaki
Steven P. Rowe
Martin G. Pomper
Constantin Lapa
Takahiro Higuchi
eng
uncontrolled
Sodium-Glucose Cotransporters (SGLTs)
eng
uncontrolled
diabetes
eng
uncontrolled
rats
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30070/Molecular_Imaging_Matsusaka.pdf
27515
2022
eng
11
14
article
1
--
2022-05-25
--
Associations between normal organs and tumor burden in patients imaged with fibroblast activation protein inhibitor-directed positron emission tomography
(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.
Cancers
2072-6694
10.3390/cancers14112609
urn:nbn:de:bvb:20-opus-275154
2022-06-05T20:35:18+00:00
sword
swordwue
attachment; filename=deposit.zip
33eb3a512dd57164847ac0634c0b8978
Cancers (2022) 14:11, 2609. doi:10.3390/cancers14112609
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Aleksander Kosmala
Sebastian E. Serfling
Niklas Dreher
Thomas Lindner
Andreas Schirbel
Constantin Lapa
Takahiro Higuchi
Andreas K. Buck
Alexander Weich
Rudolf A. Werner
eng
uncontrolled
PET
eng
uncontrolled
[\(^{68}\)Ga]Ga-FAPI
eng
uncontrolled
theranostics
eng
uncontrolled
radioligand therapy
eng
uncontrolled
fibroblast activation protein
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik II
Import
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/27515/cancers-14-02609.pdf
31876
2022
eng
1406
1412
14
82
article
1
--
--
--
Any decline in prostate-specific antigen levels identifies survivors scheduled for prostate-specific membrane antigen-directed radioligand therapy
Background
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly incorporated in the therapeutic algorithm of patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to elucidate the predictive performance of early biochemical response for overall survival (OS).
Materials and Methods
In this bicentric analysis, we included 184 mCRPC patients treated with \(^{177}\)Lu-PSMA RLT. Response to treatment was defined as decrease in prostate-specific antigen (PSA) levels 8 weeks after the first cycle of RLT (any decline or >50% according to Prostate Cancer Working Group 3). OS of responders and nonresponders was then compared using Kaplan–Meier curves and log-rank comparison.
Results
A total of 114/184 patients (62.0%) showed any PSA decline (PSA response >50%, 55/184 [29.9%]). For individuals exhibiting a PSA decline >50%, OS of 19 months was significantly longer relative to nonresponders (13 months; hazard ratio of death [HR] = 0.64, 95% confidence interval [95% CI] = 0.44–0.93; p = 0.02). However, the difference was even more pronounced for any PSA decline, with an OS of 19 months in responders, but only 8 months in nonresponders (HR = 0.39, 95% CI = 0.25–0.60; p < 0.001).
Conclusions
In mCRPC patients scheduled for RLT, early biochemical response was tightly linked to prolonged survival, irrespective of the magnitude of PSA decline. As such, even in patients with PSA decrease of less than 50%, RLT should be continued.
The Prostate
10.1002/pros.24414
urn:nbn:de:bvb:20-opus-318766
@articleHartrampf.2022, author = Hartrampf, Philipp E. and Weinzierl, Franz-Xaver and Seitz, Anna Katharina and Kübler, Hubert and Essler, Markus and Buck, Andreas K. and Werner, Rudolf A. and Bundschuh, Ralph A., year = 2022, title = Any decline in prostate-specific antigen levels identifies survivors scheduled for prostate-specific membrane antigen-directed radioligand therapy, pages = 1406–1412, volume = 82, number = 14, journal = The Prostate, doi = 10.1002/pros.24414,
md5:14a7df38de55c74f72e8f58bd2f1b95e
2023-06-06T13:51:00+00:00
/tmp/phpnSF3TY
bibtex
647f39c4d46f21.28503980
The Prostate 2022, 82(14):1406-1412. DOI: 10.1002/pros.24414
false
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Philipp E. Hartrampf
Franz-Xaver Weinzierl
Anna Katharina Seitz
Hubert Kübler
Markus Essler
Andreas K. Buck
Rudolf A. Werner
Ralph A. Bundschuh
eng
uncontrolled
prostate cancer
eng
uncontrolled
theranostics
eng
uncontrolled
PSMA‐617
eng
uncontrolled
PSA response
eng
uncontrolled
PSMA I&T
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Urologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/31876/Hartrampf_Prostate.pdf
25478
2022
eng
2
14
article
1
--
2022-01-06
--
Changing threshold-based segmentation has no relevant impact on semi-quantification in the context of structured reporting for PSMA-PET/CT
Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients imaged with \(^{18}\)F-PSMA-1007 PET/CT for primary staging and determined the stability of semi-quantitative parameters. Six hundred twenty-three lesions were categorized according to PSMA-RADS and manually segmented. In this context, PSMA-RADS-3A (soft-tissue) or -3B (bone) lesions are defined as being indeterminate for the presence of PC. For PMSA-RADS-4 and -5 lesions; however, PC is highly likely or almost certainly present [with further distinction based on absence (PSMA-RADS-4) or presence (PSMA-RADS-5) of correlative findings on CT]. Standardized uptake values (SUV\(_{max}\), SUV\(_{peak}\), SUV\(_{mean}\)) were recorded, and volumetric parameters [PSMA-derived tumor volume (PSMA-TV); total lesion PSMA (TL-PSMA)] were determined using different maximum intensity thresholds (MIT) (40 vs. 45 vs. 50%). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories (p ≤ 0.0322). In particular, the clinically challenging PSMA-RADS-3A lesions showed significantly lower SUV\(_{max}\) and SUV\(_{peak}\) compared to the entire PSMA-RADS-4 or -5 cohort (p < 0.0001), while for PSMA-RADS-3B this only applies when compared to the entire PSMA-RADS-5 cohort (p < 0.0001), but not to the PSMA-RADS-4 cohort (SUV\(_{max}\), p = 0.07; SUV\(_{peak}\), p = 0.08). SUV\(_{mean}\) (p = 0.30) and TL-PSMA (p = 0.16) in PSMA-RADS-5 lesions were not influenced by changing the MIT, while PSMA-TV showed significant differences when comparing 40 vs. 50% MIT (p = 0.0066), which was driven by lymph nodes (p = 0.0239), but not bone lesions (p = 0.15). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories in \(^{18}\)F-PSMA-1007 PET/CT. As such, the latter parameter may assist the interpreting molecular imaging specialist in assigning the correct PSMA-RADS score to sites of disease, thereby increasing diagnostic certainty. In addition, changes of the MIT in PSMA-RADS-5 lesions had no significant impact on SUV\(_{mean}\) and TL-PSMA in contrast to PSMA-TV.
Cancers
2072-6694
10.3390/cancers14020270
urn:nbn:de:bvb:20-opus-254782
2022-02-05T18:52:40+00:00
sword
swordwue
attachment; filename=deposit.zip
624b79594ef4e64412f974299caae9d7
Cancers (2022) 14:2, 270. https://doi.org/10.3390/cancers14020270
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Patrick W. Mihatsch
Matthias Beissert
Martin G. Pomper
Thorsten A. Bley
Anna K. Seitz
Hubert Kübler
Andreas K. Buck
Steven P. Rowe
Sebastian E. Serfling
Philipp E. Hartrampf
Rudolf A. Werner
eng
uncontrolled
\(^{18}\)F-PSMA-1007
eng
uncontrolled
PET/CT
eng
uncontrolled
staging
eng
uncontrolled
prostate cancer
eng
uncontrolled
standardized reporting system
eng
uncontrolled
PSMA-RADS
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik)
Urologische Klinik und Poliklinik
Import
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/25478/cancers-14-00270.pdf
27119
2022
eng
5
11
article
1
--
2022-04-26
--
Reduced segmentation of lesions is comparable to whole-body segmentation for response assessment by PSMA PET/CT: initial experience with the keyhole approach
Simple Summary
The calculation of PSMA-positive tumor volume (PSMA-TV) of the whole body from PSMA PET scans for response evaluation remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative tumor lesions. Changes in the whole-body PSMA-TV of 65 patients were comparable to the changes in PSMA-TV after including only the ten largest lesions. Moreover, changes in PSMA-TV correlated well with changes in PSA levels, as did the changes in PSMA-TV with the reduced number of lesions. We conclude that a response assessment using PSMA-TV with a reduced number of lesions is feasible and could lead to a simplified process for evaluating PSMA PET/CT.
Abstract
(1) Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-derived parameters, such as the commonly used standardized uptake value (SUV) and PSMA-positive tumor volume (PSMA-TV), have been proposed for response assessment in metastatic prostate cancer (PCa) patients. However, the calculation of whole-body PSMA-TV remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative lesions. (2) Methods: Sixty-five patients classified into different disease stages were assessed by PSMA PET/CT for staging and restaging after therapy. Whole-body PSMA-TV and whole-body SUV\(_{max}\) were calculated. We then repeated this calculation only including the five or ten hottest or largest lesions. The corresponding serum levels of prostate-specific antigen (PSA) were also determined. The derived delta between baseline and follow-up values provided the following parameters: ΔSUV\(_{maxall}\), ΔSUV\(_{max10}\), ΔSUV\(_{max5}\), ΔPSMA-TV\(_{all}\), ΔPSMA-TV\(_{10}\), ΔPSMA-TV\(_{5}\), ΔPSA. Finally, we compared the findings from our whole-body segmentation with the results from our keyhole approach (focusing on a limited number of lesions) and correlated all values with the biochemical response (ΔPSA). (3) Results: Among patients with metastatic hormone-sensitive PCa (mHSPC), none showed a relevant deviation for ΔSUV\(_{max10}\)/ΔSUV\(_{max5}\) or ΔPSMA-TV\(_{10}\)/ΔPSMA-TV\(_{5}\) compared to ΔSUV\(_{maxall}\) and ΔPSMA-TV\(_{all}\). For patients treated with taxanes, up to 6/21 (28.6%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only up to 2/21 (9.5%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). For patients treated with radioligand therapy (RLT), up to 5/28 (17.9%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only 1/28 (3.6%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). The highest correlations with ΔPSA were found for ΔPSMA-TV\(_{all}\) (r ≥ 0.59, p ≤ 0.01), followed by ΔPSMA-TV\(_{10}\) (r ≥ 0.57, p ≤ 0.01) and ΔPSMA-TV\(_{5}\) (r ≥ 0.53, p ≤ 0.02) in all cohorts. ΔPSA only correlated with ΔSUV\(_{maxall}\) (r = 0.60, p = 0.02) and with ΔSUV\(_{max10}\) (r = 0.53, p = 0.03) in the mHSPC cohort, as well as with ΔSUV\(_{maxall}\) (r = 0.51, p = 0.01) in the RLT cohort. (4) Conclusion: Response assessment using PSMA-TV with a reduced number of lesions is feasible, and may allow for a simplified evaluation process for PSMA PET/CT.
Biology
2079-7737
10.3390/biology11050660
urn:nbn:de:bvb:20-opus-271191
2022-05-09T06:54:08+00:00
sword
swordwue
attachment; filename=deposit.zip
99dad9b133f83c43d656ed4558e39a73
Biology (2022) 11:5, 660. doi:10.3390/biology11050660
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Philipp E. Hartrampf
Markus Krebs
Lea Peter
Marieke Heinrich
Julia Ruffing
Charis Kalogirou
Maximilian Weinke
Joachim Brumberg
Hubert Kübler
Andreas K. Buck
Rudolf A. Werner
Anna Katharina Seitz
eng
uncontrolled
PET/CT
eng
uncontrolled
PSMA-TV
eng
uncontrolled
SUV
eng
uncontrolled
prostate cancer
eng
uncontrolled
taxane
eng
uncontrolled
radioligand therapy
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Urologische Klinik und Poliklinik
Import
Comprehensive Cancer Center Mainfranken
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/27119/biology-11-00660.pdf
30068
2022
eng
4446
4458
9
12
article
1
--
--
--
Molecular Imaging-Derived Biomarker of Cardiac Nerve Integrity - Introducing High NET Affinity PET Probe \(^{18}\)F-AF78
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.
Theranostics
10.7150/thno.63205
urn:nbn:de:bvb:20-opus-300685
@articleChen.2022, author = Chen, Xinyu and Werner, Rudolf A. and Koshino, Kazuhiro and Nose, Naoko and Mühlig, Saskia and Rowe, Steven P. and Pomper, Martin G. and Lapa, Constantin and Decker, Michael and Higuchi, Takahiro, year = 2022, title = Molecular Imaging-Derived Biomarker of Cardiac Nerve Integrity - Introducing High NET Affinity PET Probe 18F-AF78, pages = 4446–4458, volume = 12, number = 9, journal = Theranostics, doi = 10.7150/thno.63205,
md5:fb4c26c82b049074d66c4ba92e23366f
2023-01-23T07:14:08+00:00
/tmp/phpIl8ujD
bibtex
63ce33c010fed2.40760513
Theranostics 2022, 12(9):4446-4458. DOI: 10.7150/thno.63205
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Xinyu Chen
Rudolf A. Werner
Kazuhiro Koshino
Naoko Nose
Saskia Mühlig
Steven P. Rowe
Martin G. Pomper
Constantin Lapa
Michael Decker
Takahiro Higuchi
eng
uncontrolled
norepinephrine transporter
eng
uncontrolled
T-shaped π-π stacking
eng
uncontrolled
nonhuman primates
eng
uncontrolled
radiotracer kinetics
eng
uncontrolled
cardiac innervation imaging
eng
uncontrolled
sympathetic nervous system
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Institut für Pharmazie und Lebensmittelchemie
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30068/Theranostics_Chen.pdf
30075
2022
eng
12
article
1
--
--
--
Generative adversarial network-created brain SPECTs of cerebral ischemia are indistinguishable to scans from real patients
Deep convolutional generative adversarial networks (GAN) allow for creating images from existing databases. We applied a modified light-weight GAN (FastGAN) algorithm to cerebral blood flow SPECTs and aimed to evaluate whether this technology can generate created images close to real patients. Investigating three anatomical levels (cerebellum, CER; basal ganglia, BG; cortex, COR), 551 normal (248 CER, 174 BG, 129 COR) and 387 pathological brain SPECTs using N-isopropyl p-I-123-iodoamphetamine (123I-IMP) were included. For the latter scans, cerebral ischemic disease comprised 291 uni- (66 CER, 116 BG, 109 COR) and 96 bilateral defect patterns (44 BG, 52 COR). Our model was trained using a three-compartment anatomical input (dataset ‘A’; including CER, BG, and COR), while for dataset ‘B’, only one anatomical region (COR) was included. Quantitative analyses provided mean counts (MC) and left/right (LR) hemisphere ratios, which were then compared to quantification from real images. For MC, ‘B’ was significantly different for normal and bilateral defect patterns (P < 0.0001, respectively), but not for unilateral ischemia (P = 0.77). Comparable results were recorded for LR, as normal and ischemia scans were significantly different relative to images acquired from real patients (P ≤ 0.01, respectively). Images provided by ‘A’, however, revealed comparable quantitative results when compared to real images, including normal (P = 0.8) and pathological scans (unilateral, P = 0.99; bilateral, P = 0.68) for MC. For LR, only uni- (P = 0.03), but not normal or bilateral defect scans (P ≥ 0.08) reached significance relative to images of real patients. With a minimum of only three anatomical compartments serving as stimuli, created cerebral SPECTs are indistinguishable to images from real patients. The applied FastGAN algorithm may allow to provide sufficient scan numbers in various clinical scenarios, e.g., for “data-hungry” deep learning technologies or in the context of orphan diseases.
Scientific reports
10.1038/s41598-022-23325-3
urn:nbn:de:bvb:20-opus-300757
@articleWerner.2022b, author = Werner, Rudolf A. and Higuchi, Takahiro and Nose, Naoko and Toriumi, Fujio and Matsusaka, Yohji and Kuji, Ichiei and Kazuhiro, Koshino, year = 2022, title = Generative adversarial network-created brain SPECTs of cerebral ischemia are indistinguishable to scans from real patients, pages = 18787, volume = 12, number = 1, journal = Scientific reports, doi = 10.1038/s41598-022-23325-3,
md5:9ce64593c50383a117fbaf2067e3044e
2023-01-23T07:14:08+00:00
/tmp/phpIl8ujD
bibtex
63ce33c010fed2.40760513
Scientific Reports (2022) 12:18787. https://doi.org/10.1038/s41598-022-23325-3
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Takahiro Higuchi
Naoko Nose
Fujio Toriumi
Yohji Matsusaka
Ichiei Kuji
Koshino Kazuhiro
eng
uncontrolled
computational biology and bioinformatics
eng
uncontrolled
machine learning
eng
uncontrolled
neurology
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30075/s41598-022-23325-3.pdf
30074
2022
eng
2022
article
1
--
--
--
High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with \(^{18}\)F-DCFPyL
No abstract available.
Molecular Imaging
10.1155/2022/7056983
urn:nbn:de:bvb:20-opus-300748
@articleWerner.2022, author = Werner, Rudolf A. and Habacha, Bilêl and Lütje, Susanne and Bundschuh, Lena and Higuchi, Takahiro and Hartrampf, Philipp and Serfling, Sebastian E. and Derlin, Thorsten and Lapa, Constantin and Buck, Andreas K. and Essler, Markus and Pienta, Kenneth J. and Eisenberger, Mario A. and Markowski, Mark C. and Shinehouse, Laura and AbdAllah, Rehab and Salavati, Ali and Lodge, Martin A. and Pomper, Martin G. and Gorin, Michael A. and Bundschuh, Ralph A. and Rowe, Steven P., year = 2022, title = High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with 18F-DCFPyL, pages = 7056983, volume = 2022, journal = Molecular imaging, doi = 10.1155/2022/7056983,
md5:2c45d96c81e28e57e83883b49a75b5d9
2023-01-23T07:14:08+00:00
/tmp/phpIl8ujD
bibtex
63ce33c010fed2.40760513
Molecular Imaging (2022) 2022:7056983. https://doi.org/10.1155/2022/7056983
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Bilêl Habacha
Susanne Lütje
Lena Bundschuh
Takahiro Higuchi
Philipp Hartrampf
Sebastian E. Serfling
Thorsten Derlin
Constantin Lapa
Andreas K. Buck
Markus Essler
Kenneth J. Pienta
Mario A. Eisenberger
Mark C. Markowski
Laura Shinehouse
Rehab AbdAllah
Ali Salavati
Martin A. Lodge
Martin G. Pomper
Michael A. Gorin
Ralph A. Bundschuh
Steven P. Rowe
eng
uncontrolled
SUV
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Comprehensive Cancer Center Mainfranken
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30074/7056983.pdf
30071
2022
eng
2022
article
1
--
--
--
Performance Evaluation of a Preclinical SPECT Scanner with a Collimator Designed for Medium-Sized Animals
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.
Molecular Imaging
10.1155/2022/9810097
urn:nbn:de:bvb:20-opus-300713
@articleMatsusaka.2022b, author = Matsusaka, Yohji and Werner, Rudolf A. and Arias-Loza, Paula and Nose, Naoko and Sasaki, Takanori and Chen, Xinyu and Lapa, Constantin and Higuchi, Takahiro, year = 2022, title = Performance Evaluation of a Preclinical SPECT Scanner with a Collimator Designed for Medium-Sized Animals, pages = 9810097, volume = 2022, journal = Molecular imaging, doi = 10.1155/2022/9810097,
md5:72cac27ac231904f547cec93ce22a1d8
2023-01-23T07:14:08+00:00
/tmp/phpIl8ujD
bibtex
63ce33c010fed2.40760513
Molecular Imaging 2022, Vol 2022, Article ID 9810097. DOI: 10.1155/2022/9810097
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Yohji Matsusaka
Rudolf A. Werner
Paula Arias-Loza
Naoko Nose
Takanori Sasaki
Xinyu Chen
Constantin Lapa
Takahiro Higuchi
eng
uncontrolled
SPECT Scanner
eng
uncontrolled
medium-sized animals
eng
uncontrolled
performance
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30071/Molecular_Matsuaka.pdf
25482
2022
eng
3
14
article
1
--
2022-01-27
--
Hematotoxicity and nephrotoxicity in prostate cancer patients undergoing radioligand therapy with [\(^{177}\)Lu]Lu-PSMA I&T
(1) Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) has shown remarkable results in patients with advanced prostate cancer. We aimed to evaluate the toxicity profile of the PSMA ligand [\(^{177}\)Lu]Lu-PSMA I&T. (2) Methods: 49 patients with metastatic, castration-resistant prostate cancer treated with at least three cycles of [\(^{177}\)Lu]Lu-PSMA I&T were evaluated. Prior to and after RLT, we compared leukocytes, hemoglobin, platelet counts, and renal functional parameters (creatinine, eGFR, n = 49; [\(^{99m}\)Tc]-MAG3-derived tubular extraction rate (TER), n = 42). Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and KDIGO Society. To identify predictive factors, we used Spearman's rank correlation coefficient. (3) Results: A substantial fraction of the patients already showed impaired renal function and reduced leukocyte counts at baseline. Under RLT, 11/49 (22%) patients presented with nephrotoxicity CTCAE I or II according to creatinine, but 33/49 (67%) according to eGFR. Only 5/42 (13%) showed reduced TER, defined as <70% of the age-adjusted mean normal values. Of all renal functional parameters, absolute changes of only 2% were recorded. CTCAE-based re-categorization was infrequent, with creatinine worsening from I to II in 2/49 (4.1%; GFR, 1/49 (2%)). Similar results were recorded for KDIGO (G2 to G3a, 1/49 (2%); G3a to G3b, 2/49 (4.1%)). After three cycles, follow-up eGFR correlated negatively with age (r = −0.40, p = 0.005) and the eGFR change with Gleason score (r = −0.35, p < 0.05) at baseline. Leukocytopenia CTCAE II occurred only in 1/49 (2%) (CTCAE I, 20/49 (41%)) and CTCAE I thrombocytopenia in 7/49 (14%), with an absolute decrease of 15.2% and 16.6% for leukocyte and platelet counts. Anemia CTCAE II occurred in 10/49 (20%) (CTCAE I, 36/49 (73%)) with a decrease in hemoglobin of 4.7%. (4) Conclusions: After PSMA-targeted therapy using [\(^{177}\)Lu]Lu-PSMA I&T, no severe (CTCAE III/IV) toxicities occurred, thereby demonstrating that serious adverse renal or hematological events are unlikely to be a frequent phenomenon with this agent.
Cancers
2072-6694
10.3390/cancers14030647
urn:nbn:de:bvb:20-opus-254825
2022-02-05T20:01:55+00:00
sword
swordwue
attachment; filename=deposit.zip
19d98f68c1fbbef98966177079a280ab
Cancers (2022) 14:3, 647. https://doi.org/10.3390/cancers14030647
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Philipp E. Hartrampf
Franz-Xaver Weinzierl
Sebastian E. Serfling
Martin G. Pomper
Steven P. Rowe
Takahiro Higuchi
Anna Katharina Seitz
Hubert Kübler
Andreas K. Buck
Rudolf A. Werner
eng
uncontrolled
PSMA
eng
uncontrolled
radioligand therapy
eng
uncontrolled
RLT
eng
uncontrolled
\(^{177}\)Lu
eng
uncontrolled
nephrotoxicity
eng
uncontrolled
hematotoxicity
eng
uncontrolled
CTCAE
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Urologische Klinik und Poliklinik
Import
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/25482/cancers-14-00647-v2.pdf
29051
2022
eng
2639
2647
6
8
article
1
--
2022-10-27
--
Association of true positivity with serum prostate-specific antigen levels and other clinical factors in indeterminate PSMA-RADS-3A lesions identified on \(^{18}\)F-DCFPyL PET/CT scans
The use of prostate-specific membrane antigen targeted PET imaging for the evaluation of prostate cancer has increased significantly in the last couple of decades. When evaluating these imaging findings based on the PSMA reporting and data system version 1.0, which categorize lesions based on their likelihood of prostate cancer involvement, PSMA-RADS-3A lesions are commonly seen, which are indeterminate for the presence of disease. A total of 28 patients with 171 PSMA-RADS-3A lesions on \(^{18}\)F-DCFPyL PET/CT scans from June 2016 to May 2017 who had follow-up cross-sectional imaging over time were included in this study. The PSA levels of patients with PSMA-RADS-3A lesions were categorized into four groups, 0–0.2, 0.2–1, 1–2, and >2 ng/mL. The pre-operative Gleason score of these patients was categorized into two groups, Gleason score < 7 or ≥7. The median age for these patients was 72.5 years (range 59–81). The median PSA value for patients with positive lesions was significantly higher than those with negative lesions (5.8 ng/mL vs. 0.2 ng/mL, p < 0.0001). The lesion positivity rate was significantly higher in patients with PSA > 1 ng/mL (18.2% vs. 81.9%, p < 0.001). On ROC analysis, the highest classification accuracy was seen at PSA ≥ 0.6 ng/mL of 80.12% (95% CI = 73.69–86.16%), and the area under the curve was 71.32% (95% CI = 61.9–80.7%, p < 0.0001). A total of 96.4% (108/112) of patients with positive lesions and 86.4% (51/59) of patients with negative lesions had a PSMA-RADS-4/5 lymph node on the initial \(^{18}\)F-DCFPyL PET/CT scan (p = 0.02). In patients with a Gleason score ≥ 7, the presence of positive PSMA-RADS-3A lesions was higher, compared to negative PSMA-RADS-3A lesions (p = 0.049). Higher PSA levels in patients with PSMA-RADS-3A lesions can point towards the presence of true positivity. PSA levels may be considered in deciding whether to call an indeterminate lesion on PSMA PET.
Tomography
2379-139X
10.3390/tomography8060220
urn:nbn:de:bvb:20-opus-290510
2022-11-04T14:44:32+00:00
sword
swordwue
attachment; filename=deposit.zip
7dd92d4a39797ba9ab814f104adb3594
Tomography (2022) 8:6, 2639-2647. https://doi.org/10.3390/tomography8060220
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Tushar Garg
Rudolf A. Werner
Hyun Woo Chung
Wajahat Khatri
Kenneth J. Pienta
Martin G. Pomper
Michael A. Gorin
Elie Saad
Steven P. Rowe
eng
uncontrolled
prostate cancer
eng
uncontrolled
prostate-specific antigen
eng
uncontrolled
PSMA-RADS
eng
uncontrolled
\(^{18}\)F-DCFPyL PET/CT
eng
uncontrolled
Gleason score
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/29051/tomography-08-00220.pdf
32392
2022
eng
3661-3669
8
407
article
1
--
--
--
Questionable value of [\(^{99m}\)Tc]-sestamibi scintigraphy in patients with pHPT and negative ultrasound
Purpose
A successful focused surgical approach in primary hyperparathyroidism (pHPT) relies on accurate preoperative localization of the parathyroid adenoma (PA). Most often, ultrasound is followed by [\(^{99m}\)Tc]-sestamibi scintigraphy, but the value of this approach is disputed. Here, we evaluated the diagnostic approach in patients with surgically treated pHPT in our center with the aim to further refine preoperative diagnostic procedures.
Methods
A single-center retrospective analysis of patients with pHPT from 01/2005 to 08/2021 was carried out followed by evaluation of the preoperative imaging modalities to localize PA. The localization of the PA had to be confirmed intraoperatively by the fresh frozen section and significant dropping of the intraoperative parathyroid hormone (PTH) levels.
Results
From 658 patients diagnosed with pHPT, 30 patients were excluded from the analysis because of surgery for recurrent or persistent disease. Median age of patients was 58.0 (13–93) years and 71% were female. Neck ultrasound was carried out in 91.7% and localized a PA in 76.6%. In 23.4% (135/576) of the patients, preoperative neck ultrasound did not detect a PA. In this group, [\(^{99m}\)Tc]-sestamibi correctly identified PA in only 25.4% of patients. In contrast, in the same cohort, the use of [\(^{11}\)C]-methionine or [\(^{11}\)C]-choline PET resulted in the correct identification of PA in 79.4% of patients (OR 13.23; 95% CI 5.24–33.56).
Conclusion
[\(^{11}\)C]-Methionine or [\(^{11}\)C]-choline PET/CT are superior second-line imaging methods to select patients for a focused surgical approach when previous ultrasound failed to identify PA.
Langenbeck’s Archives of Surgery
10.1007/s00423-022-02648-9
urn:nbn:de:bvb:20-opus-323926
@articleLenschow.2022, author = Lenschow, Christina and Wennmann, Andreas and Hendricks, Anne and Germer, Christoph-Thomas and Fassnacht, Martin and Buck, Andreas and Werner, Rudolf A. and Plassmeier, Lars and Schlegel, Nicolas, year = 2022, title = Questionable value of 99mTc-sestamibi scintigraphy in patients with pHPT and negative ultrasound, pages = 3661–3669, volume = 407, number = 8, journal = Langenbeck’s archives of surgery, doi = 10.1007/s00423-022-02648-9
md5:1f364d0bed64702ee387e94b700a4a52
2023-08-12T09:01:06+00:00
/tmp/phpvihHh5
bibtex
64d74a5205a688.90874886
Langenbeck’s Archives of Surgery (2022) 407:8, 3661-3669 DOI: 10.1007/s00423-022-02648-9
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Christina Lenschow
Andreas Wennmann
Anne Hendricks
Christoph-Thomas Germer
Martin Fassnacht
Andreas Buck
Rudolf A. Werner
Lars Plassmeier
Nicolas Schlegel
eng
uncontrolled
primary hyperparathyroidism
eng
uncontrolled
parathyroid adenoma
eng
uncontrolled
[99mTc]-Sestamibi scan
eng
uncontrolled
[11C]-Methionine
eng
uncontrolled
[11C]-Choline PET/CT
eng
uncontrolled
focused surgical approach
Chirurgie und verwandte medizinische Fachrichtungen
open_access
Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I)
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/32392/s00423-022-02648-9.pdf
32462
2022
eng
659-665
4
24
article
1
--
--
--
Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT
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.
Molecular Imaging and Biology
10.1007/s11307-022-01717-1
urn:nbn:de:bvb:20-opus-324622
@articleSerfling.2022, author = Serfling, Sebastian E. and Lapa, Constantin and Dreher, Niklas and Hartrampf, Philipp E. and Rowe, Steven P. and Higuchi, Takahiro and Schirbel, Andreas and Weich, Alexander and Hahner, Stefanie and Fassnacht, Martin and Buck, Andreas K. and Werner, Rudolf A., year = 2022, title = Impact of Tumor Burden on Normal Organ Distribution in Patients Imaged with CXCR4-Targeted 68GaGa-PentixaFor PET/CT, pages = 659–665, volume = 24, number = 4, journal = Molecular imaging and biology, doi = 10.1007/s11307-022-01717-1
md5:e03754a5b52653c92b708583aeba78cf
2023-08-12T10:37:25+00:00
/tmp/phpKtPjJc
bibtex
64d760e520e2f0.54800151
Molecular Imaging and Biology (2022) 24:4, 659-665 DOI: 10.1007/s11307-022-01717-1
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Sebastian E. Serfling
Constantin Lapa
Niklas Dreher
Philipp E. Hartrampf
Steven P. Rowe
Takahiro Higuchi
Andreas Schirbel
Alexander Weich
Stefanie Hahner
Martin Fassnacht
Andreas K. Buck
Rudolf A. Werner
eng
uncontrolled
CXCR4
eng
uncontrolled
C-X-C motif chemokine receptor 4
eng
uncontrolled
PET
eng
uncontrolled
[68Ga]PentixaFor
eng
uncontrolled
[177Lu]/[90Y]PentixaTher
eng
uncontrolled
theranostics
eng
uncontrolled
endoradiotherapy
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/32462/s11307-022-01717-1.pdf
32464
2022
eng
631-640
4
24
article
1
--
--
--
Training on reporting and data system (RADS) for somatostatin-receptor targeted molecular imaging can reduce the test anxiety of inexperienced readers
Purpose
For somatostatin receptor (SSTR)-positron emission tomography/computed tomography (PET/CT), a standardized framework termed SSTR-reporting and data system (RADS) has been proposed. We aimed to elucidate the impact of a RADS-focused training on reader’s anxiety to report on SSTR-PET/CT, the motivational beliefs in learning such a system, whether it increases reader’s confidence, and its implementation in clinical routine.
Procedures
A 3-day training course focusing on SSTR-RADS was conducted. Self-report questionnaires were handed out prior to the course (Pre) and thereafter (Post). The impact of the training on the following categories was evaluated: (1) test anxiety to report on SSTR-PET/CT, (2) motivational beliefs, (3) increase in reader’s confidence, and (4) clinical implementation. To assess the effect size of the course, Cohen’s d was calculated (small, d = 0.20; large effect, d = 0.80).
Results
Of 22 participants, Pre and Post were returned by 21/22 (95.5%). In total, 14/21 (66.7%) were considered inexperienced (IR, < 1 year experience in reading SSTR-PET/CTs) and 7/21 (33.3%) as experienced readers (ER, > 1 year). Applying SSTR-RADS, a large decrease in anxiety to report on SSTR-PET/CT was noted for IR (d = − 0.74, P = 0.02), but not for ER (d = 0.11, P = 0.78). For the other three categories motivational beliefs, reader’s confidence, and clinical implementation, agreement rates were already high prior to the training and persisted throughout the course (P ≥ 0.21).
Conclusions
A framework-focused reader training can reduce anxiety to report on SSTR-PET/CTs, in particular for inexperienced readers. This may allow for a more widespread adoption of this system, e.g., in multicenter trials for better intra- and interindividual comparison of scan results.
Molecular Imaging and Biology
10.1007/s11307-022-01712-6
urn:nbn:de:bvb:20-opus-324645
@articleWeich.2022, author = Weich, Alexander and Higuchi, Takahiro and Bundschuh, Ralph A. and Lapa, Constantin and Serfling, Sebastian E. and Rowe, Steven P. and Pomper, Martin G. and Herrmann, Ken and Buck, Andreas K. and Derlin, Thorsten and Werner, Rudolf A., year = 2022, title = Training on Reporting and Data System (RADS) for Somatostatin-Receptor Targeted Molecular Imaging Can Reduce the Test Anxiety of Inexperienced Readers, pages = 631–640, volume = 24, number = 4, journal = Molecular imaging and biology, doi = 10.1007/s11307-022-01712-6
md5:cbf6bcfa88ba2960624db078d2f727c9
2023-08-12T10:37:25+00:00
/tmp/phpKtPjJc
bibtex
64d760e520e2f0.54800151
Molecular Imaging and Biology (2022) 24:4, 631-640. DOI: 10.1007/s11307-022-01712-6
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander Weich
Takahiro Higuchi
Ralph A. Bundschuh
Constantin Lapa
Sebastian E. Serfling
Steven P. Rowe
Martin G. Pomper
Ken Herrmann
Andreas K. Buck
Thorsten Derlin
Rudolf A. Werner
eng
uncontrolled
PET/CT
eng
uncontrolled
neuroendocrine tumor
eng
uncontrolled
PRRT
eng
uncontrolled
peptide receptor radionuclide therapy
eng
uncontrolled
reporting and data system
eng
uncontrolled
SSTR-RADS
eng
uncontrolled
RADS
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/32464/s11307-022-01712-6.pdf
32461
2022
eng
228-229
1
50
article
1
--
--
--
CXCR4-targeted molecular imaging after severe SARS-Cov-2 infection
No abstract available.
European Journal of Nuclear Medicine and Molecular Imaging
10.1007/s00259-022-05932-4
urn:nbn:de:bvb:20-opus-324619
@articleLambertini.2022, author = Lambertini, Alessandro and Hartrampf, Philipp E. and Higuchi, Takahiro and Serfling, Sebastian E. and Meybohm, Patrick and Schirbel, Andreas and Buck, Andreas K. and Werner, Rudolf A., year = 2022, title = CXCR4-targeted molecular imaging after severe SARS-Cov-2 infection, pages = 228–229, volume = 50, number = 1, journal = European journal of nuclear medicine and molecular imaging, doi = 10.1007/s00259-022-05932-4
md5:db819afdfb66ddf438b0bb4a29f31620
2023-08-12T10:37:25+00:00
/tmp/phpKtPjJc
bibtex
64d760e520e2f0.54800151
European Journal of Nuclear Medicine and Molecular Imaging (2022) 50:1, 228-229 DOI: 10.1007/s00259-022-05932-4
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alessandro Lambertini
Philipp E. Hartrampf
Takahiro Higuchi
Sebastian E. Serfling
Patrick Meybohm
Andreas Schirbel
Andreas K. Buck
Rudolf A. Werner
eng
uncontrolled
CXCR4-targeting
eng
uncontrolled
SARS-CoV-2
eng
uncontrolled
COVID-19
eng
uncontrolled
molecular imaging
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/32461/s00259-022-05932-4.pdf
32457
2022
eng
4262-4270
12
49
article
1
--
--
--
Baseline clinical characteristics predict overall survival in patients undergoing radioligand therapy with [\(^{177}\)Lu]Lu-PSMA I&T during long-term follow-up
Background
Radioligand therapy (RLT) with \(^{177}\)Lu-labeled prostate-specific membrane antigen (PSMA) ligands is associated with prolonged overall survival (OS) in patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). A substantial number of patients, however, are prone to treatment failure. We aimed to determine clinical baseline characteristics to predict OS in patients receiving [\(^{177}\)Lu]Lu-PSMA I&T RLT in a long-term follow-up.
Materials and methods
Ninety-two mCRPC patients treated with [\(^{177}\)Lu]Lu-PSMA I&T with a follow-up of at least 18 months were retrospectively identified. Multivariable Cox regression analyses were performed for various baseline characteristics, including laboratory values, Gleason score, age, prior therapies, and time interval between initial diagnosis and first treatment cycle (interval\(_{Diagnosis-RLT}\), per 12 months). Cutoff values for significant predictors were determined using receiver operating characteristic (ROC) analysis. ROC-derived thresholds were then applied to Kaplan–Meier analyses.
Results
Baseline C-reactive protein (CRP; hazard ratio [HR], 1.10, 95% CI 1.02–1.18; P = 0.01), lactate dehydrogenase (LDH; HR, 1.07, 95% CI 1.01–1.11; P = 0.01), aspartate aminotransferase (AST; HR, 1.16, 95% CI 1.06–1.26; P = 0.001), and interval\(_{Diagnosis-RLT}\) (HR, 0.95, 95% CI 0.91–0.99; P = 0.02) were identified as independent prognostic factors for OS. The following respective ROC-based thresholds were determined: CRP, 0.98 mg/dl (area under the curve [AUC], 0.80); LDH, 276.5 U/l (AUC, 0.83); AST, 26.95 U/l (AUC, 0.73); and interval\(_{Diagnosis-RLT}\), 43.5 months (AUC, 0.68; P < 0.01, respectively). Respective Kaplan–Meier analyses demonstrated a significantly longer median OS of patients with lower CRP, lower LDH, and lower AST, as well as prolonged interval\(_{Diagnosis-RLT}\) (P ≤ 0.01, respectively).
Conclusion
In mCRPC patients treated with [\(^{177}\)Lu]Lu-PSMA I&T, baseline CRP, LDH, AST, and time interval until RLT initiation (thereby reflecting a possible indicator for tumor aggressiveness) are independently associated with survival. Our findings are in line with previous findings on [\(^{177}\)Lu]Lu-PSMA-617, and we believe that these clinical baseline characteristics may support the nuclear medicine specialist to identify long-term survivors.
European Journal of Nuclear Medicine and Molecular Imaging
10.1007/s00259-022-05853-2
urn:nbn:de:bvb:20-opus-324573
@articleHartrampf.2022b, author = Hartrampf, Philipp E. and Seitz, Anna Katharina and Weinzierl, Franz-Xaver and Serfling, Sebastian E. and Schirbel, Andreas and Rowe, Steven P. and Kübler, Hubert and Buck, Andreas K. and Werner, Rudolf A., year = 2022, title = Baseline clinical characteristics predict overall survival in patients undergoing radioligand therapy with 177LuLu-PSMA I&T during long-term follow-up, pages = 4262–4270, volume = 49, number = 12, journal = European journal of nuclear medicine and molecular imaging, doi = 10.1007/s00259-022-05853-2
md5:cb8e015224adb66ea9718fbe3bebf40a
2023-08-12T10:37:25+00:00
/tmp/phpKtPjJc
bibtex
64d760e520e2f0.54800151
European Journal of Nuclear Medicine and Molecular Imaging (2022) 49:12, 4262-4270. DOI: 10.1007/s00259-022-05853-2
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Philipp E. Hartrampf
Anna Katharina Seitz
Franz-Xaver Weinzierl
Sebastian E. Serfling
Andreas Schirbel
Steven P. Rowe
Hubert Kübler
Andreas K. Buck
Rudolf A. Werner
eng
uncontrolled
PSMA
eng
uncontrolled
prostate cancer
eng
uncontrolled
[177Lu]Lu-PSMA I&T
eng
uncontrolled
radioligand therapy
eng
uncontrolled
overall survival
eng
uncontrolled
prediction
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Urologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/32457/s00259-022-05853-2.pdf