14779
2016
eng
78
6
article
1
2017-05-05
--
--
Impact of \(^{68}\)Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy
Background
Salvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced \(^{68}\)Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning.
Forty-five patients with PSA persistence (16 pts) or BCR (29 pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent \(^{68}\)Ga-PSMA PET/CT. The median PSA level was 0.67 ng/ml. The impact of \(^{68}\)Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity.
Results
Suspicious lesions were detected in 24/45 (53.3 %) patients. In 62.5 % of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2 %) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4 %) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78 ± 19 %) within a mean follow-up of 8.12 ± 5.23 months.
Conclusions
\(^{68}\)Ga-PSMA PET/CT impacts treatment planning in more than 40 % of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT.
EJNMMI Research
10.1186/s13550-016-0233-4
urn:nbn:de:bvb:20-opus-147798
EJNMMI Research (2016) 6:78 DOI 10.1186/s13550-016-0233-4
Christina Bluemel
Fraenze Linke
Ken Herrmann
Iva Simunovic
Matthias Eiber
Christian Kestler
Andreas K. Buck
Andreas Schirbel
Thorsten A. Bley
Hans-Juergen Wester
Daniel Vergho
Axel Becker
eng
uncontrolled
prostate cancer
eng
uncontrolled
salvage radiotherapy
eng
uncontrolled
PSMA
eng
uncontrolled
PET/CT
eng
uncontrolled
recurrence
Krankheiten
open_access
Klinik und Poliklinik für Nuklearmedizin
Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik)
Urologische Klinik und Poliklinik
Förderzeitraum 2016
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14779/Bluemel_10.1186_s13550-016-0233-4.pdf
14660
2016
eng
140
13
article
1
2017-03-31
--
--
Combined [\(^{18}\)F]DPA-714 micro-positron emission tomography and autoradiography imaging of microglia activation after closed head injury in mice
Background
Traumatic brain injury (TBI) is a major cause of death and disability. Neuroinflammation contributes to acute damage after TBI and modulates long-term evolution of degenerative and regenerative responses to injury. The aim of the present study was to evaluate the relationship of microglia activation to trauma severity, brain energy metabolism, and cellular reactions to injury in a mouse closed head injury model using combined in vivo PET imaging, ex vivo autoradiography, and immunohistochemistry.
Methods
A weight-drop closed head injury model was used to produce a mixed diffuse and focal TBI or a purely diffuse mild TBI (mTBI) in C57BL6 mice. Lesion severity was determined by evaluating histological damage and functional outcome using a standardized neuroscore (NSS), gliosis, and axonal injury by immunohistochemistry. Repeated intra-individual in vivo μPET imaging with the specific 18-kDa translocator protein (TSPO) radioligand [\(^{18}\)F]DPA-714 was performed on day 1, 7, and 16 and [\(^{18}\)F]FDG-μPET imaging for energy metabolism on days 2–5 after trauma using freshly synthesized radiotracers. Immediately after [\(^{18}\)F]DPA-714-μPET imaging on days 7 and 16, cellular identity of the [\(^{18}\)F]DPA-714 uptake was confirmed by exposing freshly cut cryosections to film autoradiography and successive immunostaining with antibodies against the microglia/macrophage marker IBA-1.
Results
Functional outcome correlated with focal brain lesions, gliosis, and axonal injury. [\(^{18}\)F]DPA-714-μPET showed increased radiotracer uptake in focal brain lesions on days 7 and 16 after TBI and correlated with reduced cerebral [\(^{18}\)F]FDG uptake on days 2–5, with functional outcome and number of IBA-1 positive cells on day 7. In autoradiography, [\(^{18}\)F]DPA-714 uptake co-localized with areas of IBA1-positive staining and correlated strongly with both NSS and the number of IBA1-positive cells, gliosis, and axonal injury. After mTBI, numbers of IBA-1 positive cells with microglial morphology increased in both brain hemispheres; however, uptake of [\(^{18}\)F]DPA-714 was not increased in autoradiography or in μPET imaging.
Conclusions
[\(^{18}\)F]DPA-714 uptake in μPET/autoradiography correlates with trauma severity, brain metabolic deficits, and microglia activation after closed head TBI.
Journal of Neuroinflammation
10.1186/s12974-016-0604-9
urn:nbn:de:bvb:20-opus-146606
Journal of Neuroinflammation (2016) 13:140 DOI 10.1186/s12974-016-0604-9
680966
Ina Israel
Andrea Ohsiek
Ehab Al-Momani
Christiane Albert-Weissenberger
Christian Stetter
Stine Mencl
Andreas K. Buck
Christoph Kleinschnitz
Samuel Samnick
Anna-Leena Sirén
eng
uncontrolled
neuroinflammation
eng
uncontrolled
TBI
eng
uncontrolled
immunohistochemistry
eng
uncontrolled
weight drop
eng
uncontrolled
PET
eng
uncontrolled
diffuse
eng
uncontrolled
focal
eng
uncontrolled
TSPO
eng
uncontrolled
autoradiography
eng
uncontrolled
IBA-1
Medizin und Gesundheit
open_access
Neurochirurgische Klinik und Poliklinik
Klinik und Poliklinik für Nuklearmedizin
Physiologisches Institut
Neurologische Klinik und Poliklinik
OpenAIRE
Förderzeitraum 2016
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14660/Israel_10.1186_s12974-016-0604-9.pdf
17731
2016
eng
41233-41241
27
7
article
1
2019-02-26
--
--
The impact of \(^{177}\)Lu-octreotide therapy on \(^{99m}\)Tc-MAG3 clearance is not predictive for late nephropathy
Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of \(^{99m}\)Tc-mercaptoacetyltriglycine (\(^{99m}\)Tc-MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6±0.4 GBq \(^{177}\)Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 ± 53 ml/min/1.73 m² before PRRT (baseline) and 221 ± 45 ml/min/1.73 m² after a median follow-up of 370 days. The age-corrected decrease (mean: -3%, range: -27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=-0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by \(^{99m}\)Tc-MAG3clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy.
Oncotarget
10.18632/oncotarget.9775
urn:nbn:de:bvb:20-opus-177318
Oncotarget 2016, 7:27, 41233-41241. DOI: 10.18632/oncotarget.9775
false
true
Rudolf A. Werner
Seval Beykan
Takahiro Higuchi
Katharina Lückerath
Alexander Weich
Michael Scheurlen
Christina Bluemel
Ken Herrmann
Andreas K. Buck
Michael Lassmann
Constantin Lapa
Heribert Hänscheid
eng
uncontrolled
renal scintigraphy
eng
uncontrolled
neuroendocrine tumor
eng
uncontrolled
177Lu
eng
uncontrolled
MAG3
eng
uncontrolled
PRRT
Pharmakologie, Therapeutik
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17731/Werner_Oncotarget.pdf
16817
2016
eng
428-434
3
6
article
1
2018-09-12
--
--
\(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma
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.
Theranostics
10.7150/thno.13986
urn:nbn:de:bvb:20-opus-168174
Theranostics 2016, Vol. 6, Issue 3, 428-434. DOI: 10.7150/thno.13986
false
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Constantin Lapa
Katharina Lückerath
Irene Kleinlein
Camelia Maria Monoranu
Thomas Linsenmann
Almuth F. Kessler
Martina Rudelius
Saskia Kropf
Andreas K. Buck
Ralf-Ingo Ernestus
Hans-Jürgen Wester
Mario Löhr
Ken Herrmann
eng
uncontrolled
imaging
eng
uncontrolled
chemokine receptor-4
eng
uncontrolled
glioblastoma
eng
uncontrolled
positron emission tomography/computed tomography
eng
uncontrolled
\(^{68}\)Ga-Pentixafor
Medizin und Gesundheit
open_access
Neurochirurgische Klinik und Poliklinik
Klinik und Poliklinik für Nuklearmedizin
Pathologisches Institut
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16817/Lapa_Theranostics.pdf