Pilot Comparison of 68Ga-RM2 PET and 68Ga-PSMA PET in Patients with Biochemically Recurrent Prostate Cancer (original) (raw)
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Cancers, 2022
Simple Summary Prostate cancer (PCa) relapse occurs in up to 50% of patients after radical treatment. Once PCa recurrence is detected, a precise identification of the number and sites of recurrence is necessary to tailor the treatment on the patient’s needs. Positron emission tomography (PET) plays a pivotal role in this clinical setting and new radiotracers have been developed to improve its performance. While 68Ga-PSMA is a well-established radiotracer for PCa recurrence detection, 68Ga-DOTA-RM2 is a recently proposed tracer that targets the gastrin-releasing peptide receptors that are overexpressed in prostate cancer. In this work, the performance of 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in identifying recurrent disease were compared on the same cohort, using the same study protocol, as this is the only way to assess whether one outperforms the other and therefore should be preferred in clinical practice. Furthermore, the association between PET findings and clinical and histopatho...
Clinical Impact of 68Ga-PSMA PET/CT in a Patient With Biochemical Recurrence of Prostate Cancer
Clinical nuclear medicine, 2016
A 64-year-old man with history of prostate adenocarcinoma underwent radical prostatectomy in 2003. He remained with undetectable prostate-specific antigen (PSA) levels until 2014, when he then presented rising serum PSA levels and performed a Tc-MDP bone scan that was negative for metastases. In August 2015, his PSA was 4.89 ng/dL, and restaging images with pelvic MR and F-FDG PET/CT were both negative. Therefore, the patient underwent a Ga-PSMA PET/CT that showed marked tracer uptake in a single mediastinal lymph node. Histopathology demonstrated metastatic adenocarcinoma secondary to prostate cancer, altering patient management to hormone therapy instead of pelvic radiotherapy.
Journal of Nuclear Medicine, 2017
The aim of this retrospective study was to evaluate the detection rate of Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)] (68 Ga-PSMA ligand; PSMA is prostate-specific membrane antigen) PET/CT in patients with biochemical recurrent prostate cancer defined by Phoenix criteria after external-beam radiotherapy or brachytherapy as primary treatment. Methods: One hundred eighteen patients with a median prostate-specific antigen (PSA) of 6.4 ng/mL (range, 2.2-158.4 ng/mL; interquartile range, 4.2-10.2 ng/mL) were finally eligible for this retrospective analysis. Seventy-seven and 41 patients had been treated by external-beam radiotherapy or brachytherapy, respectively. Of the 118 patients, 45 were receiving androgen-deprivation therapy (ADT) within at least 6 mo before the PET/CT. The detection rates were stratified by PSA. The influence of primary Gleason score and ADT was assessed. Relationships between SUV and clinical as well as pathologic features in patients with positive findings were analyzed using univariate and multivariable linear regression models. Results: One hundred seven of 118 patients (90.7%) showed pathologic findings indicative for tumor recurrence in 68 Ga-PSMA ligand PET/CT. The detection rates were 81.8% (36/44), 95.3% (41/43), and 96.8% (30/31) for PSA of 2 to ,5, 5 to ,10, and 10ng/mL,respectively(P50.0377).68Ga−PSMAligandPET/CTindicatedlocalrecurrencein68of107patients(63.510 ng/mL, respectively (P 5 0.0377). 68 Ga-PSMA ligand PET/CT indicated local recurrence in 68 of 107 patients (63.5%), distant lesions in 64 of 107 patients (59.8%), and local recurrence as well as distant lesions in 25 of 107 patients (23.4%). The detection rate was significantly higher in patients with ADT (97.7%) versus without ADT (86.3%, P 5 0.0381), but independent from primary Gleason score 10ng/mL,respectively(P50.0377).68Ga−PSMAligandPET/CTindicatedlocalrecurrencein68of107patients(63.5 8 (92.0%) versus # 7 (90.2%, P 5 0.6346). SUV max and SUV mean were significantly associated with PSA and ADT (P 5 0.018 and 0.004 for SUV max , respectively; P 5 0.025 and 0.007 for SUV mean , respectively). Conclusion: 68 Ga-PSMA ligand PET/CT demonstrates high detection rates in patients with biochemical recurrence of prostate cancer after primary radiation therapy. The detection rate was positively associated to increasing PSA as well as concomitant ADT. 68 Ga-PSMA ligand PET/CT enables discrimination of local versus metastatic disease and thus might have a crucial impact on further clinical management. A major limitation of this study is the lack of histopathologic proof in most patients.
Nuclear Medicine and Biology, 2020
Introduction: Peptide-based imaging agents targeting prostate-specific membrane antigen (PSMA) have revolutionized the evaluation of biochemical recurrence of prostate cancer (PCa) but lacks sensitivity at very low serum prostate specific antigen (PSA) levels. Once recurrence is suspected, other positron emission tomography (PET) radiotracers could be of interest to discriminate between local and distant relapse. We studied [ 18 F] fluorodeoxyglucose ([ 18 F]FDG) targeting glucose metabolism, [ 18 F]fluorocholine ([ 18 F]FCH) targeting membrane metabolism and peptide-based imaging agents [ 68 Ga]Ga-PSMA-11, [ 68 Ga]Ga-AMBA, [ 68 Ga]Ga-NODAGA-RGD and [ 68 Ga]Ga-DOTA-NT-20.3 targeting PSMA, gastrin releasing peptide receptor (GRPr), αvβ3 integrin and neurotensin type 1 receptor (NTSR1) respectively, in different PCa tumour models. Methods: Mice were xenografted with 22Rv1, an androgen-receptor (AR)-positive, PCa cell line that expresses PSMA and PC3, an AR-negative one that does not express PSMA. PET imaging using the different radiotracers was performed sequentially and the uptake characteristics compared to one other. NTSR1 and PSMA expression levels were analysed in tumours by immunohistochemistry. Results: [ 18 F]FDG displayed low but sufficient uptake to visualize PC3 and 22Rv1 derived tumours. We also observed a low efficacy of [ 18 F]FCH PET imaging and a low [ 68 Ga]Ga-NODAGA-RGD tumour uptake in those tumours. As expected, an elevated tumour uptake was obtained for [ 68 Ga]Ga-PSMA-11 in 22Rv1 derived tumour although no uptake was measured in the androgen independent cell line PC3, derived from a bone metastasis of a high-grade PCa. Moreover, in PC3 cell line, we obtained good tumour uptake, high tumour-to-background contrast using [ 68 Ga]Ga-AMBA and [ 68 Ga]Ga-DOTA-NT-20.3. Immunohistochemistry analysis confirmed high NTSR1 expression in PC3 derived tumours and conversely high PSMA expression in 22Rv1 derived tumours. Conclusion: PET imaging using [ 68 Ga]Ga-AMBA and [ 68 Ga]Ga-DOTA-NT-20.3 demonstrates that GRPr and NTSR1 could represent viable alternative targets for diagnostic or therapeutic applications in PCa with limited PSMA expression levels. More preclinical and clinical studies will follow to explore this potential. Advances in knowledge and implications for patient: Peptide-based imaging agents targeting PSMA represent a major progress in the evaluation of biochemical recurrence of PCa but sometimes yield false negative results in some lesions. Continuing efforts have thus been made to evaluate other radiotracers. Our preclinical results suggest that [ 68 Ga]labelled bombesin and neurotensin analogues could serve as alternative PET radiopharmaceuticals for diagnostic or therapy in cases of PSMA-negative PCa.
Journal of Nuclear Medicine
68 Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH 2 (68 Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptor (GRPr). GRPr proteins are highly overexpressed in several human tumors, including prostate cancer (PCa). We present data from the use of 68 Ga-RM2 in patients with biochemical recurrence (BCR) of PCa and negative findings on conventional imaging. Methods: We enrolled 32 men with BCR of PCa, who were 59-83 y old (mean ± SD, 68.7 ± 6.4 y). Imaging started at 40-69 min (mean, 50.5 ± 6.8 min) after injection of 133.2-151.7 MBq (mean, 140.6 ± 7.4 MBq) of 68 Ga-RM2 using a time-of-flight-enabled simultaneous PET/MRI scanner. T1-weighted, T2-weighted, and diffusion-weighted images were acquired. Results: All patients had a rising level of prostate-specific antigen (PSA) (range, 0.3-119.0 ng/mL; mean, 10.1 ± 21.3 ng/mL) and negative findings on conventional imaging (CT or MRI, and a 99m Tc-methylene diphosphonate bone scan) before enrollment. The observed 68 Ga-RM2 PET detection rate was 71.8%. 68 Ga-RM2 PET identified recurrent PCa in 23 of the 32 participants, whereas the simultaneous MRI scan identified findings compatible with recurrent PCa in 11 of the 32 patients. PSA velocity was 0.32 ± 0.59 ng/mL/y (range, 0.04-1.9 ng/mL/y) in patients with negative PET findings and 2.51 ± 2.16 ng/mL/y (range, 0.13-8.68 ng/mL/y) in patients with positive PET findings (P 5 0.006). Conclusion: 68 Ga-RM2 PET can be used for assessment of GRPr expression in patients with BCR of PCa. High uptake in multiple areas compatible with cancer lesions suggests that 68 Ga-RM2 is a promising PET radiopharmaceutical for localization of disease in patients with BCR of PCa and negative findings on conventional imaging.
[68Ga]Ga-PSMA-11 in prostate cancer: a comprehensive review
American journal of nuclear medicine and molecular imaging, 2020
Imaging of the prostate-specific membrane antigen (PSMA) has become an important tool for managing patients with recurrent prostate cancer, and one of the most frequently employed radiopharmaceuticals is [68Ga]Ga-PSMA-11. Herein, we summarize the preclinical development and the clinical applications of [68Ga]Ga-PSMA-11 and present side-by-side comparisons with other radiopharmaceuticals or imaging modalities, in order to assist imagers and clinicians in recommending, performing, and interpreting the results of [68Ga]Ga-PSMA-11 PET scans in patients with prostate cancer.
Cancer imaging : the official publication of the International Cancer Imaging Society, 2017
68Ga-labelled prostate specific membrane antigen (PSMA) ligand PET/CT is a promising modality in primary staging (PS) and biochemical relapse (BCR) of prostate cancer (PC). However, pelvic nodes or local recurrences can be difficult to differentiate from radioactive urine. CT urography (CT-U) is an established method, which allows assessment of urological malignancies. The study presents a novel protocol of 68Ga-PSMA-11 PET/CT-U in PS and BCR of PC. A retrospective review of PSMA PET/CT-U preformed on 57 consecutive patients with prostate cancer. Fifty mL of IV contrast was administered 10 min (range 8-15) before the CT component of a combined PET/CT study, acquired approximately 60 min (range 40-85) after administration of 166 MBq (range 91-246) of 68Ga-PSMA-11. PET and PET/CT-U were reviewed by two nuclear medicine physicians and CT-U by a radiologist. First, PET images were reviewed independently followed by PET/CT-U images. Foci of activity which could not unequivocally be asses...
Asia-Pacific journal of clinical oncology, 2021
OBJECTIVE PSMA PET/CT has demonstrated superior sensitivity over conventional imaging in the detection of local and distant recurrence in biochemically relapsed (BCR) prostate cancer. We prospectively investigated the management impact of 68 Ga-PSMA PET/CT imaging in men with BCR, with the aim of identifying baseline clinicopathological predictors for management change. PATIENTS AND METHODS Men with BCR who met eligibility criteria underwent 68 Ga-PSMA-11 PET/CT at Monash Health (Melbourne, Australia). Intended management plans were prospectively documented before and after 68 Ga-PSMA PET/CT imaging. Binary logistic regression analysis was performed to identify potential clinicopathological predictors of management change. Descriptive statistics were used to characterize the nature of these changes. RESULTS Seventy men underwent 68 Ga-PSMA-11 PET/CT imaging. Median age was 67 years (IQR 63-72) and median PSA was 0.48 ng/ml (IQR 0.21-1.9). PSMA-avid disease was observed in 56% (39/70...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2017
Purpose: In this prospective survey of referring physicians, we investigated whether and how Gallium-68 Prostate Specific Membrane Antigen Positron Emission Tomography/Computed Tomography (PSMA-11 PET/CT) affects the actually implemented management of prostate cancer patients wih biochemical recurrence (BCR). Methods: We conducted a prospective survey of physicians (NCT02940262) who referred 161 patients with prostate cancer BCR (median Prostate Specific Antigen (PSA) value 1.7 ng/ml (range 0.05-202)). Referring physicians completed one questionnaire prior to the scan to indicate the treatment plan without PSMA-11 PET/CT information (Q1; n = 101); one immediately after the scan to denote intended management changes (Q2; n = 101); and one 3 to 6 months later to document the final implemented management (Q3; n = 56). Implemented management was also obtained via electronic chart review and/or patient contact (n = 45). Results: Complete documented management strategy (Q1+Q2+implemented ...
European Journal of Nuclear Medicine and Molecular Imaging, 2019
Objectives Aim of the present analysis is to investigate the biodistribution and pharmacokinetics of the recently clinically introduced radioligand 18 F-PSMA-1007 in patients with biochemical recurrence or progression of prostate cancer (PC) by means of multiparametric (dynamic and whole-body) PET/CT. Methods Twenty-five (25) patients with PC biochemical relapse or progression (median age = 66.0 years) were enrolled in the analysis. The median PSA value was 1.2 ng/mL (range = 0.1-237.3 ng/mL) and the median Gleason score was 7 (range = 6-10). All patients underwent dynamic PET/CT (dPET/CT) scanning (60 min) of the pelvis and lower abdomen as well as whole-body PET/CT with 18 F-PSMA-1007. PET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and fractal analysis. Results 15/25 patients were PET-positive. Plasma PSA values in the 18 F-PSMA-1007 positive group were higher (median = 3.6 ng/mL; range = 0.2-237.3 ng/mL) than in the 18 F-PSMA-1007 negative group (median value = 0.7 ng/mL; range = 0.1-3.0 ng/mL). Semi-quantitative analysis in the PC lesions demonstrated a mean SUV average = 25.1 (median = 15.4; range = 3.5-119.2) and a mean SUV max = 41.5 (median = 25.7; range = 3.8-213.2). Time-activity curves derived from dPET/CT revealed an increasing tracer accumulation during the 60 min of dynamic PET acquisition into the PC lesions, higher than in the urinary bladder and the colon. Significant correlations were observed between 18 F-PSMA-1007 uptake (SUV), influx, and fractal dimension (FD). Conclusions 18 F-PSMA-1007 PET/CT could detect PC lesions in 60% of the patients of a mixed population, including also patients with very low PSA values. Higher PSA values were associated with a higher detection rate. Dynamic PET analysis revealed an increasing tracer uptake during the dynamic PET acquisition as well as high binding and internalization of the radiofluorinated PSMA ligand in the PC lesions.