scholarly journals Kinetic analysis and optimisation of 18F-rhPSMA-7.3 PET imaging of prostate cancer

Author(s):  
Simona Malaspina ◽  
Vesa Oikonen ◽  
Anna Kuisma ◽  
Otto Ettala ◽  
Kalle Mattila ◽  
...  

Abstract Purpose This phase 1 open-label study evaluated the uptake kinetics of a novel theranostic PET radiopharmaceutical, 18F-rhPSMA-7.3, to optimise its use for imaging of prostate cancer. Methods Nine men, three with high-risk localised prostate cancer, three with treatment-naïve hormone-sensitive metastatic disease and three with castration-resistant metastatic disease, underwent dynamic 45-min PET scanning of a target area immediately post-injection of 300 MBq 18F-rhPSMA-7.3, followed by two whole-body PET/CT scans acquired from 60 and 90 min post-injection. Volumes of interest (VoIs) corresponding to prostate cancer lesions and reference tissues were recorded. Standardised uptake values (SUV) and lesion-to-reference ratios were calculated for 3 time frames: 35–45, 60–88 and 90–118 min. Net influx rates (Ki) were calculated using Patlak plots. Results Altogether, 44 lesions from the target area were identified. Optimal visual lesion detection started 60 min post-injection. The 18F-rhPSMA-7.3 signal from prostate cancer lesions increased over time, while reference tissue signals remained stable or decreased. The mean (SD) SUV (g/mL) at the 3 time frames were 8.4 (5.6), 10.1 (7) and 10.6 (7.5), respectively, for prostate lesions, 11.2 (4.3), 13 (4.8) and 14 (5.2) for lymph node metastases, and 4.6 (2.6), 5.7 (3.1) and 6.4 (3.5) for bone metastases. The mean (SD) lesion-to-reference ratio increases from the earliest to the 2 later time frames were 40% (10) and 59% (9), respectively, for the prostate, 65% (27) and 125% (47) for metastatic lymph nodes and 25% (19) and 32% (30) for bone lesions. Patlak plots from lesion VoIs signified almost irreversible uptake kinetics. Ki, SUV and lesion-to-reference ratio estimates showed good agreement. Conclusion 18F-rhPSMA-7.3 uptake in prostate cancer lesions was high. Lesion-to-background ratios increased over time, with optimal visual detection starting from 60 min post-injection. Thus, 18F-rhPSMA-7.3 emerges as a very promising PET radiopharmaceutical for diagnostic imaging of prostate cancer. Trial Registration NCT03995888 (24 June 2019).

2021 ◽  
Author(s):  
Teli Liu ◽  
Chen Liu ◽  
Zhongyi Zhang ◽  
Ning Zhang ◽  
Xiaoyi Guo ◽  
...  

Abstract PurposeDevelop a 64Cu labeled radiopharmaceutical targeting prostate specific membrane antigen (PSMA) and investigate its application for prostate cancer imaging. Methods64Cu-PSMA-BCH was prepared and investigated for stability, PSMA specificity and micro-PET imaging. With the approval of Ethics Committee of Beijing Cancer Hospital (No. 2017KT97), PET/CT imaging in 4 patients with suspected prostate cancer was performed and the radiation dosimetry was estimated. Then, PSMA PET-ultrasound image-guided biopsies were performed on 3 patients and the fine needle aspirates were further performed for autoradiography and immunohistochemistry analysis. Results64Cu-PSMA-BCH was prepared with high radiochemical yield and stability. In vivo study showed higher uptake in PSMA (+) 22Rv1 cells than PSMA (-) PC-3 cells (5.59±0.36 and 1.97±0.22 IA%/106 cells at 1 h). It accumulated in 22Rv1 tumor with increasing radioactivity uptake and T/N ratios from 1 h to 24 h post-injection. In patients with suspected prostate cancer, SUVmax and T/N ratios increased within 24 h post-injection. Compared with image at 1 h post-injection, more tumor lesions were detected at 4 h and 24 h post-injection. The human organ radiation dosimetry showed gallbladder wall was most critical, liver and kidneys were followed, and the whole-body effective dose was 0.0292 mSv/MBq. Two fine needle aspirates obtained by PET-ultrasound guided targeted biopsy showed high radioactive signal by autoradiography, with 100% PSMA expression in cytoplasm and 30% expression in nucleus. Conclusion64Cu-PSMA-BCH was PSMA specific and showed high stability in vivo with lower uptake in liver than 64Cu-PSMA-617. Biodistribution in mice and PCa patients showed similar profile compared with other PSMA ligands and it was safe with moderate effective dosimetry. The increased tumor uptake and T/N ratios by delayed imaging may facilitate the detection of small lesions and guiding targeted biopsies.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Paola Pricolo ◽  
Eleonora Ancona ◽  
Paul Summers ◽  
Jorge Abreu-Gomez ◽  
Sarah Alessi ◽  
...  

Abstract Background The METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P) guidelines are designed to enable reproducible assessment in detecting and quantifying metastatic disease response using whole-body magnetic resonance imaging (WB-MRI) in patients with advanced prostate cancer (APC). The purpose of our study was to evaluate the inter-observer agreement of WB-MRI examination reports produced by readers of different expertise when using the MET-RADS-P guidelines. Methods Fifty consecutive paired WB-MRI examinations, performed from December 2016 to February 2018 on 31 patients, were retrospectively examined to compare reports by a Senior Radiologist (9 years of experience in WB-MRI) and Resident Radiologist (after a 6-months training) using MET-RADS-P guidelines, for detection and for primary/dominant and secondary response assessment categories (RAC) scores assigned to metastatic disease in 14 body regions. Inter-observer agreement regarding RAC score was evaluated for each region by using weighted-Cohen’s Kappa statistics (K). Results The number of metastatic regions reported by the Senior Radiologist (249) and Resident Radiologist (251) was comparable. For the primary/dominant RAC pattern, the agreement between readers was excellent for the metastatic findings in cervical, dorsal, and lumbosacral spine, pelvis, limbs, lungs and other sites (K:0.81–1.0), substantial for thorax, retroperitoneal nodes, other nodes and liver (K:0.61–0.80), moderate for pelvic nodes (K:0.56), fair for primary soft tissue and not assessable for skull due to the absence of findings. For the secondary RAC pattern, agreement between readers was excellent for the metastatic findings in cervical spine (K:0.93) and retroperitoneal nodes (K:0.89), substantial for those in dorsal spine, pelvis, thorax, limbs and pelvic nodes (K:0.61–0.80), and moderate for lumbosacral spine (K:0.44). Conclusions We found inter-observer agreement between two readers of different expertise levels to be excellent in bone, but mixed in other body regions. Considering the importance of bone metastases in patients with APC, our results favor the use of MET-RADS-P in response to the growing clinical need for monitoring of metastasis in these patients.


1999 ◽  
pp. 392
Author(s):  
Ralph Oberneder ◽  
Marc Steinborn ◽  
Melanie Bruegel ◽  
Alfons Hofstetter ◽  
Maximilian Reiser

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 158-158
Author(s):  
Tejas Suresh ◽  
Qi Gao ◽  
Mimi Kim ◽  
Sanjay Goel ◽  
Benjamin Adam Gartrell

158 Background: In the United States, prostate cancer (PCa) incidence and death rate differ among racial groups. Non-Hispanic Blacks (NHB) have a higher incidence and death rate than non-Hispanic Whites (NHW), whereas incidence and death rate are slightly lower in Hispanics (H) than in NHW. We sought to compare the socioeconomic, demographic and baseline prognostic factors at PCa diagnosis among different races at a large, urban academic center serving a diverse population. Methods: Following institutional review board approval, the Montefiore Medical Center Cancer Registry was used to generate a comprehensive list of patients diagnosed with PCa 2004 to 2013. Clinical Looking Glass (a searchable database of patient information) and individual patient chart review were used to obtain data including age at diagnosis, socioeconomic score (SES), Gleason score, stage at diagnosis and PSA at diagnosis. Patients were classified by self-identified race as H, NHB or NHW. For categorical variables the chi-square test was used, whereas the ANOVA or the Kruskal-Wallis tests were employed for continuous variables. Results: During the specified period 2352 patients were diagnosed with PCa among which 778 were self-classified as H, 1046 as NHB, 486 as NHW and 42 as other (O). The mean age at diagnosis differed between these groups (H 63.2, NHB 63.4, NHW 67, O 63.0, p < 0.0001). The proportion of men below the mean SES also differed between races (H 92.8%, NHB 91.3%, NHW 56.6%, O 75%, p < 0.0001). Median PSA (ng/ml) at diagnosis was similar (H 8.0, NHB 8.4 NHW 7.2, O 6.4, p = 0.0768) whereas Gleason score differed between racial groups (Gleason ≤ 6: H 42.8%, NHB 39.1%, NHW 52.2%, O 50%; Gleason 8-10: H 15.8%, NHB 17.6%, NHW 14.3%, O 16.7%, p = 0.0005). The proportion of men with metastatic disease at diagnosis also differed significantly in these groups (H 7.5%, NHB 9.0%, NHW 4.3%, O 9.5%, p = 0.0139). Conclusions: At our center, in patients with newly diagnosed PCa, there are significant differences among racial groups. These include age at diagnosis, SES, Gleason score and proportion with metastatic disease. Such differences at diagnosis suggest that minority patients are at risk for inferior PCa outcomes.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 206-206
Author(s):  
Katia Ramos Moreira Leite ◽  
Manuel Garcia Florez ◽  
Sabrina Thalita Reis ◽  
Nayara Viana ◽  
Betina S. Katz ◽  
...  

206 Background: Prostate cancer (PC) depends on the androgen activity being the androgen blockage the main treatment in the setting of metastatic disease. Mechanisms of resistance in metastatic tumors are not completely known. MicroRNAs (miRNA) are small non-coding molecules that have as canonical mechanism the negative control of gene expression promoting messenger RNA (mRNA) degradation or impairing protein translation. The role of miRNAs that have as target the AR are still unknown. Our objective is to study the expression profile of miRNAs that have AR as target in localized prostate cancer. Methods: The expression levels of miRNAs that have as target AR (miR9, 34a, 34c, 185, 130a, 299, 421, 371, 541) were studied using qRT-PCR in the surgical specimens of 83 patients that underwent radical prostatectomy to treat localized prostate cancer. The expression levels of miRNAs were correlated to Gleason score (GS), pre-operatory PSA, pathological stage and biochemical recurrence (PSA>0.2 ng/mL) in a mean follow up of 45.9 months. The mean age was 62.9, mean GS was 7.2, mean PSA was 7.93 ng/mL, and 42 (50.6%) patients were staged pT2. Twenty-four (28.9%) patients presented biochemical recurrence. Specimens of six patients submitted to open surgery to treat benign prostate hyperplasia (BPH) composed the control group. Results: The mean expression of AR was 1.63, being overexpressed in 59% of the cases. The mean expression levels of the nine studied miRNAs was miR9=3.06, miR34a=0.76, miR34c=1.14, miR185=1.65, miR130a=1.9, miR299=6.23, miR421=2.84, miR371=1.41, and miR541=0.93. The univariate analysis showed that pT2 tumors have higher expression of miR371(p=0.009). Conclusions: In localized PC the higher expression of miR371 is related with organ-confined disease. This miRNA could be important in the control of AR and the comprehension of its role in PC might bring alternatives to treat metastatic disease. Funded by FAPESP – 2012/50163-0.


2021 ◽  
Author(s):  
Jiaying Zhang ◽  
Zefang Lin ◽  
Xiaojun Zhang ◽  
Rong Lin ◽  
Mengchao Cui ◽  
...  

Abstract PurposeThis prospective trial aimed to evaluate the safety, dosimetry, biodistribution, and diagnostic efficacy of a novel theranostic probe 68Ga-DOTA-DiPSMA. Also, we have performed the first comparison with 68Ga-PSMA-11 in prostate cancer (PCa) patients.MethodsFive healthy volunteers and ten PCa patients with a previous clinical 68Ga-PSMA-11 PET/CT were injected with an intravenous bolus of 68Ga-DOTA-DiPSMA with a dose of 1.85MBq/kg. Healthy volunteers received serial whole-body PET scans from the time of injection up to 60 min post-injection, with a second PET/CT scanning at 120 min post-injection. In PCa patients, low-dose CT scan, whole-body PET was performed with 2 min per bed position in 40 min post-injection. In addition, 68Ga-PSMA-11 scanning was performed on PCa patients within 10 days under the same acquisition procedure. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake and tumor lesion uptake (SUVmax) were measured. A lesion-by-lesion analysis was performed.Results68Ga-DOTA-DiPSMA administration was safe and well-tolerated. The kidneys received the highest absorbed dose (114.46 ± 29.28 uSv/MBq), followed by the urinary bladder wall (100.82 ± 46.22 uSv/MBq) in accordance with the expected PSMA renal excretion of the tracer. The mean effective dose was 19.46 ± 1.73 μSv/MBq. The SUVmax of 68Ga-PSMA-11 and 68Ga-DOTA-DiPSMA PET/CT for PCa lesions, bone metastases, and lymph node metastases were 11.2 ± 10.76 vs. 4.41 ± 2.72, 7.6 ± 1.58 vs. 2.95 ± 1.11 and 4.86 ± 1.94 vs. 3.26 ± 1.2, respectively.ConclusionInjection of 68Ga-DOTA-DiPSMA is safe and associated with low absorbed and effective doses. Compared to 68Ga-PSMA-11, 68Ga-DOTA-DiPSMA shows comparable pharmacokinetics and detection ability in PCa patients that warrant further head-to-head comparison. Low non-specific uptake in salivary glands and kidneys of 68Ga-DOTA-DiPSMA indicates potential radioligand therapy (RLT) application when labeled with 177Lu, 90Y, or 225Ac.


2010 ◽  
Vol 49 (04) ◽  
pp. 148-153 ◽  
Author(s):  
A. Rominger ◽  
T. Saam ◽  
S. Wolpers ◽  
K. Nikolaou ◽  
P. Cumming ◽  
...  

Summary Aim: Fluorine-labelled choline derivatives were recently suggested as agents for visualizing vulnerable atherosclerotic plaques. We therefore aimed to evaluate the association between18F-fluoroethylcholine (FEC) uptake in the wall of large arteries, where calcification was also measured, with the presence of cardiovascular risk factors and occurrence of prior cardiovascular events. Patients, methods: Detailed clinical information, including common cardiovascular risk factors, was obtained retrospectively in 60 prostate cancer patients examined with whole-body FEC PETCT. In each patient, we calculated the mean blood pool-corrected SUV, as well as the mean target-to-background ratio (TBR), in addition to the sum of calcified plaques (CPsum) from six major vessels: ascending and descending aorta, aortic arch, abdominal aorta, and both iliac arteries. Results: As reported previously, the CPsum correlated significantly with cardiovascular risk factors, in contrast to mean SUV or TBR scores, which did not show any significance with the presence of cardiovascular risk factors. There was no correlation between CPsum, mean TBR or SUV, nor was there any significant association of CPsum, mean TBR or SUV with the prior occurrence of cardio- or cerebrovascular events. Conclusion: Contrary to a recent report, we found in our rather large cohort of elderly prostate cancer patients no significant association between FEC uptake in large vessels and atherosclerotic plaque burden, or the presence of cardiovascular risk factors. In line with prior reports on structural changes in vessels, increased calcified atherosclerotic plaque burden was strongly associated with the occurrence of common cardiovascular risk factors.


Radiology ◽  
2015 ◽  
Vol 275 (1) ◽  
pp. 155-166 ◽  
Author(s):  
Vasiliki Pasoglou ◽  
Nicolas Michoux ◽  
Frank Peeters ◽  
Ahmed Larbi ◽  
Bertrand Tombal ◽  
...  

2021 ◽  
pp. 20210403
Author(s):  
Parul Thakral ◽  
Ishita Sen ◽  
Subha Shankar Das ◽  
Divya Manda ◽  
Virupakshappa CB ◽  
...  

Objective: The aim of the present study was to perform calculation of the absorbed doses to organs at risk and to neuroendocrine tumors and to determine whether hepatic intra-arterial (IA) injection of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) would achieve higher intratumoral concentrations than standard intravenous administration of 177Lu-DOTATATE. Methods: 29 patients with Grade I-II, inoperable, metastatic gastro-entero-pancreatic neuroendocrine tumor (GEPNET) were prospectively identified and enrolled for the study. 15 patients of GEPNETs with liver-dominant metastatic disease and less than 3 sites of extrahepatic metastatic disease were administered a single dose of 177Lu-DOTATATE therapy through the selective catheterization of the hepatic artery (IA group). The other 14 patients received a single dose of 177 Lu- DOTATATE through standard intravenous route (IV group). For dosimetry, whole-body γ (anterior and posterior planar acquisitions) and SPECT/CT scans of the abdomen at 2, 24 and 96 h post 177Lu-DOTATATE administration were acquired. Dosimetric calculations were done using the HERMES software. Results: The mean dose per unit activity (DpA) in the liver and tumor lesions in the IA group differed significantly (p < 0.05) but differed insignificantly in spleen and kidneys (p > 05) with the IV group. The mean tumor/non-tumor concentration at 96 h was 76.83 ± 7.9 (range 10.2–251.3) in the IA group whereas it was 25.6 ± 5.9 (Range: 12–55) in the IV group. There was an average threefold increase in tumoral concentration over the standard intravenous group. Conclusion: IA administration of 177Lu-DOTATATE results in higher concentration and absorbed dose in hepatic metastases in patients of GEPNETs as compared to a single dose of PRRT administered through standard IV route, and thus seems to be a powerful tool to improve the efficacy of PRRT. Advances in knowledge: Measurement of the dose received by the tumor lesions and the critical organs is of paramount importance for the prognostication of a radionuclide therapy. Scant data exist on the dosimetric impact of IA administration of the therapy with 177Lu-DOTATATE on the tumors and other organs, and this study would add an impact towards the better treatment outcome in patients of neuroendocrine tumor with liver-dominant metastatic disease.


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