Prostate-specific Membrane Antigen Uptake Research Articles

The future of PSMA PET and WB MRI as next-generation imaging tools in prostate cancer

Radiolabelled prostate-specific membrane antigen (PSMA)-based PET-CT has been shown in numerous studies to be superior to conventional imaging in the detection of nodal or distant metastatic lesions. 68Ga-PSMA PET-CT is now recommended by many guidelines for the detection of biochemically relapsed disease after radical local therapy. PSMA radioligands can also function as radiotheranostics, and Lu-PSMA has been shown to be a potential new line of treatment for metastatic castration-resistant prostate cancer. Whole-body (WB) MRI has been shown to have a high diagnostic performance in the detection and monitoring of metastatic bone disease. Prospective, randomized, multicentre studies comparing 68Ga-PSMA PET-CT and WB MRI for pelvic nodal and metastatic disease detection are yet to be performed. Challenges for interpretation of PSMA include tracer trapping in non-target tissues and also urinary excretion of tracers, which confounds image interpretation at the vesicoureteral junction. Additionally, studies have shown how long-term androgen deprivation therapy (ADT) affects PSMA expression and could, therefore, reduce tracer uptake and visibility of PSMA+ lesions. Furthermore, ADT of short duration might increase PSMA expression, leading to the PSMA flare phenomenon, which makes the accurate monitoring of treatment response to ADT with PSMA PET challenging. Scan duration, detection of incidentalomas and presence of metallic implants are some of the major challenges with WB MRI. Emerging data support the wider adoption of PSMA PET and WB MRI for diagnosis, staging, disease burden evaluation and response monitoring, although their relative roles in the standard-of-care management of patients are yet to be fully defined.

F-18 PSMA Uptake in Male Breast Cancer during Restaging Evaluation of Carcinoma Prostate.

Fluorine-18 prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography scan is widely used for restaging of prostate cancer. We present a case where false-positive PSMA uptake was seen in metachronous carcinoma breast during restaging workup of carcinoma prostate.

A Case Report: Application of 68Ga-PSMA-PET/CT for the Diagnosis of Bone Metastases in Patients with Low Prostate-Specific Antigen Levels

Prostate cancer is the second most common type of cancer in men worldwide. It is one of the 5 most common cancer types and contributes to the greatest number of deaths among male patients. It is most common for prostate cancer to metastasize to the vertebrae, ribs, and pelvis. An important determinant of bone metastasis is the level of prostate-specific membrane antigen (PSMA). The risk of metastatic disease is low in patients who have low serum prostate-specific antigen (PSA) levels. This study examined a patient with suspected bone metastasis based on computed tomography (CT), which is considered to be a rare condition, but whose PSA level was abnormally low. 68Ga-PSMA-PET/CT scans were performed on the patient. It was discovered that bone metastases had developed in several regions of the patients’ body. Several sclerotic lesions were observed in the lumbar vertebrae and bilateral iliac wings, suggesting that bone metastases had occurred. An examination of the pelvis revealed a lesion exhibiting Ga-68 PSMA uptake, with a SUVmax of 4.97. Furthermore, laps with Ga-68 PSMA involvement with SUVmax: 8.65 could also be seen in the paracaval and aortokaval regions.

Feasibility of biology-guided radiotherapy using PSMA-PET to boost to dominant intraprostatic tumour

BackgroundBiology-guided radiotherapy (BgRT) delivers dose to tumours triggered from positron emission tomography (PET) detection. Prostate specific membrane antigen (PSMA) PET uptake is abundant in the dominant intraprostatic lesion (DIL). This study investigates the feasibility of BgRT to PSMA-avid subvolume in the prostate region. MethodsPatients enrolled in the prospective randomized trial ProPSMA at our institution were included (ID: ANZCTR12617000005358). Gross tumour volumes (GTVs) were delineated on the PET component of a PET/CT scan from a standardized uptake value (SUV) threshold technique. Suitability for BgRT requires a strong signal-to-background ratio with a surrounding tissue free of significant PSMA uptake. The signal-to-background ratio was quantified from the calculation of the normalized SUV (nSUV), defined as the ratio between SUVmax within the GTV and SUVmean inside a 3D margin expansion of the GTV. The PSMA distribution surrounding the tumour was quantified as a function of the distance from the GTV. ResultsIn this cohort of 84 patients, 83 primary tumours were included. Prostate volume ranged from 19 cm3 to 148 cm3 (median = 52 cm3; IQR = 39 cm3 – 63 cm3). SUVmax inside the prostate was between 2 and 125 (median = 19; IQR = 11 – 30). More than 50% of GTVs generated with threshold between 25%SUVmax (median volume = 10.0 cm3; IQR = 4.5 cm3 – 20.0 cm3) and 50%SUVmax (median volume = 1.9 cm3; IQR = 1.1 cm3 – 3.8 cm3) were suitable for BgRT by using nSUV ≥ 3 and a margin expansion of 5 mm. ConclusionsIt is feasible to identify GTVs suitable for BgRT in the prostate. These GTVs are characterized by a strong signal-to-background ratio and a surrounding tissue free of PSMA uptake.

Optimization of ODAP-Urea-based dual-modality PSMA targeting probes for sequential PET-CT and optical imaging

Prostate-specific membrane antigen (PSMA) is emerging as a promising target to specifically image prostate cancer. Dual-modality probe combining radionuclide imaging and near-infrared fluorescence navigation targeting PSMA would enable both the preoperative staging and intraoperative detection of the tumor lesions. To overcome one of the key barriers for achieving high contrast imaging at both early and late time points, we optimized the pharmacokinetics of dual-modality probes based on oxalyldiaminopropionic acid-urea (ODAP-Urea) PSMA inhibitors recently developed. Four dual-modality probes with variable hydrophilicity were synthesized and evaluated. They displayed good optical properties (λem max = 835 nm, QY = 0.67%-1.50%), high affinity to PSMA (Ki = 2.09 ± 1.71–4.15 ± 2.20 nM) and PSMA specific cellular uptake (0.48 ± 0.01% − 0.64 ± 0.04% IA/105 LNCaP cells) upon labeled with 68Ga. In vivo studies showed that [68Ga]Ga-P3 exhibited an optimum pharmacokinetic property with high specific tumor uptake (SUVmax = 1.88 ± 0.36, at 1 h) in medium level PSMA expressing 22Rv1 tumor model and high tumor-to-muscle ratio (12.56 ± 2.63, at 1 h). Specific fluorescence imaging could also be achieved with high contrast for later time points (tumor-to-background ratio = 11.63 ± 4.16 at 24 h). This study demonstrates that ODAP-Urea-based P3 has the potential for PET imaging and intraoperative optical imaging of prostate cancer.

MP09-20 PROSTATE BIOPSY TARGETED TO PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) FOCI

You have accessJournal of UrologyCME1 May 2022MP09-20 PROSTATE BIOPSY TARGETED TO PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) FOCI David Kuppermann, Jeremie Calais, Wayne Brisbane, Elizabeth Tran, Lorna Herbert, Matthias Benz, Johannes Czernin, and Leonard Marks David KuppermannDavid Kuppermann More articles by this author , Jeremie CalaisJeremie Calais More articles by this author , Wayne BrisbaneWayne Brisbane More articles by this author , Elizabeth TranElizabeth Tran More articles by this author , Lorna HerbertLorna Herbert More articles by this author , Matthias BenzMatthias Benz More articles by this author , Johannes CzerninJohannes Czernin More articles by this author , and Leonard MarksLeonard Marks More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002531.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: PSMA PET imaging is the most accurate imaging method known for detection of metastatic PCa. PSMA PET may also reveal intra-prostatic cancer. 68Ga-PSMA scanning was approved by FDA in December 2020 for pre-op staging of PCa and to detect possible recurrence. MRI-guided biopsy (MRGB) is the preferred method for diagnosis of prostate cancer (PCa), but PCa may be MRI-invisible (≈15-20%). Herein we study intra-prostatic PSMA focal uptake as a target for biopsy detection of PCa using PET/CT-US fusion (PSMA-guided biopsy, PSMA-GB). METHODS: In a prospective trial, 13 men underwent PSMA PET/CT imaging prior to fusion biopsy at UCLA. Subjects are men with negative prior biopsy (10 MRGB), but continued clinical suspicion of PCa and focal uptake of PSMA in the prostate. Method of PSMA-GB is identical to MRGB (PMID 26749141) but employs US fusion with PET/CT instead of MRI, as detailed previously (PMID: 28607878). Method of Ga-PSMA image acquisition via PET/CT scanning has been reported (PMID: 30920593). Contouring of intra-prostatic foci of PSMA positivity was via Profuse software by co-author J.C. Image fusion & trans-rectal targeted biopsy was via Artemis device (LSM). Detection rate of csPCa ( >GG2) by PSMA-GB was primary endpoint. RESULTS: To date, 13 men have completed study. Median age=71 yrs.; prostate volume=27.7 cc (IQR 22.1, 38.3); PSA density=0.25 ng/ml/cc (IQR 0.10, 0.45 PSMA-GB was successfully completed in all 13 with no more difficulty than usual MRI-GB. Overall detection rate was 9/13 (70%): GG2 in 1, GG3 in 6, and GG4 in 2. Max Cancer Core Length was 4 mm median (IQR 3, 9). 4 PSMA foci were anterior; all 4 contained csPCa. Median SUVmax (standardized uptake value) was 6 in PSMA lesions returning <GG1 findings vs 8.2 in men with csPCa. Median PSAD (density) was higher in men with csPCa (0.25) than others (0.20). Of 5 men with prior radiation, 4 had csPCa on PSMA-GB. CONCLUSIONS: Prostate biopsy, which targets PSMA “hot spots” via PET/CT-US fusion, may lead to detection of clinically significant cancers missed by MRI-guided biopsy. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e144 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Kuppermann More articles by this author Jeremie Calais More articles by this author Wayne Brisbane More articles by this author Elizabeth Tran More articles by this author Lorna Herbert More articles by this author Matthias Benz More articles by this author Johannes Czernin More articles by this author Leonard Marks More articles by this author Expand All Advertisement PDF DownloadLoading ...

Infiltrative growth pattern of prostate cancer is associated with lower uptake on PSMA PET and reduced diffusion restriction on mpMRI

PurposeRecently, a significant association was shown between novel growth patterns on histopathology of prostate cancer (PCa) and prostate-specific membrane antigen (PSMA) uptake on [68Ga]PSMA-PET. It is the aim of this study to evaluate the association between these growth patterns and ADC (mm2/1000 s) values in comparison to [68Ga]PSMA uptake on PET/MRI.MethodsWe retrospectively evaluated patients who underwent [68Ga]PSMA PET/MRI for staging or biopsy guidance, followed by radical prostatectomy at our institution between 07/2016 and 01/2020. The dominant lesion per patient was selected based on histopathology and correlated to PET/MRI in a multidisciplinary meeting, and quantified using SUVmax for PSMA uptake and ADCmean for diffusion restriction. PCa growth pattern was classified as expansive (EXP) or infiltrative (INF) according to its properties of forming a tumoral mass or infiltrating diffusely between benign glands by two independent pathologists. Furthermore, the corresponding WHO2016 ISUP tumor grade was evaluated. The t test was used to compare means, Pearson’s test for categorical correlation, Cohen’s kappa test for interrater agreement, and ROC curve to determine the best cutoff.ResultsSixty-two patients were included (mean PSA 11.7 ± 12.5). The interrater agreement between both pathologists was almost perfect with κ = 0.81. While 25 lesions had an EXP-growth with an ADCmean of 0.777 ± 0.109, 37 showed an INF-growth with a significantly higher ADCmean of 1.079 ± 0.262 (p < 0.001). We also observed a significant difference regarding PSMA SUVmax for the EXP-growth (19.2 ± 10.9) versus the INF-growth (9.4 ± 6.2, p < 0.001). Within the lesions encompassing the EXP- or the INF-growth, no significant correlation between the ISUP groups and ADCmean could be observed (p = 0.982 and p = 0.861, respectively).ConclusionPCa with INF-growth showed significantly lower SUVmax and higher ADCmean values compared to PCa with EXP-growth. Within the growth groups, ADCmean values were independent from ISUP grading.

18F-Prostate-Specific Membrane Antigen and 18F-Fluorodeoxyglucose PET/CT Unmasked the Characteristics of Prostate Lymphoma: A Case Report and Literature Review

Prostate lymphoma (PL) is rarely observed and may be concurrently presented with prostate adenocarcinoma. Moreover, the appearance of PL on conventional imaging is similar with prostate adenocarcinoma. Thus, most of PL is diagnosed through prostate biopsy, or accidentally found in the specimens of surgery. Prostate-specific membrane antigen (PSMA) PET/CT has improved the management of prostate adenocarcinoma. While, the question regarding whether it benefits the discovery of the characteristics of PL is unknown. A 32-year-old man presented with worsening dysuria for 1 month, and the prostate-specific antigen (PSA) concentration was normal. While the pelvic MRI showed a mass in the prostate and multiple enlarged lymph nodes in the bilateral inguinal area. Then, the diagnosis of prostate adenocarcinoma was considered, but the serum PSA was normal and he was younger than most patients. So, 18F-PSMA PET/CT was then performed to further reveal the characteristics of the lesion and guide biopsy. However, there was no abnormal PSMA uptake in the lesion of the prostate and lymph nodes of the pelvic cavity and bilateral inguinal area. These lesions presented with increased glucose metabolism on fluorodeoxyglucose (FDG) PET/CT, and the prostate biopsy was then performed. PL was confirmed based on the results of the histopathologic examination, and the patient subsequently received systemic chemotherapy plus radiotherapy. Fortunately, the symptoms and the lesions completely disappeared after radiotherapy. The clinical symptoms of PL are atypical, and PL and adenocarcinoma may be concurrently presented. Moreover, distinguishing PL from prostate adenocarcinoma based on the appearance of conventional imaging is difficult. As opposed to prostate adenocarcinoma, a high FDG-avidity and low PSMA uptake by lymphoma either in the prostate or metastases are seen. So, PSMA PET/CT combined with FDG PET/CT can non-invasively identify the characteristics and origin of PL.

Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates.

Purpose: to evaluate a unique subpopulation of radical prostatectomy (RP) candidates with “negative” prostate 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) imaging scans and to characterize the clinical implications of misleading findings. Materials and Methods: This case-control retrospective study compared the final histological outcomes of patients with “negative” pre-RP PSMA PET/CT prostate scans (with a prostate maximal standardized uptake value [SUVmax] below the physiologic uptake) to those with an “intense” prostatic tracer uptake (with a SUVmax above the physiologic uptake). The patients underwent an RP between March 2015 and July 2019 in five academic centers. Data on the demographics, comorbidities, prostate-specific antigen (PSA) and rectal exam findings, prior biopsies, imaging results, biopsies, and RP histology results were collected. Results: Ninety-seven of the 392 patients who underwent an RP had PSMA PET/CT imaging preoperatively. Fifty-two (54%) had a “negative” uptake (in the study group), and 45 (46%) had a “positive” uptake (in the control group). Only the lesion size and SUVmax values on the PSMA PET/CT differed between the groups preoperatively. On the histological analysis, only the ISUP score, seminal vesicles invasion, T stage, and positive margin rates differed between the groups (p < 0.05), while 50 (96%) study group patients harbored clinically significant disease (ISUP ≥ 2), with an extra-prostatic disease in 24 (46%), perineural invasion in 35 (67%), and positive lymph nodes in 4 (8%). Conclusions: Disease aggressiveness generally correlated with an intense PSMA uptake on the preoperative PSMA PET/CT, but a subpopulation of patients with clinically significant cancer and aggressive characteristics showed a deceptively weak PSMA uptake. These data raise a concern about the unqualified application of PSMA PET/CT for staging RP candidates.

Clinical and molecular features of low prostate-specific membrane antigen (PSMA) expression in patients (pts) with metastatic castration resistant prostate cancer (mCRPC).

167 Background: Low PSMA uptake on positron-emission tomography is seen in up to 30% of mCRPC pts and represents a clinically distinct subgroup with adverse outcomes. We assessed transcriptional and clinical features associated with low PSMA ( FOLH1) gene expression in mCRPC. Methods: A retrospective analysis of mCRPC biopsy samples with RNA-seq data was undertaken. Normalized FOLH1 expression was compared across histologic subtypes and sites of disease. We assessed the association between FOLH1 expression, selected androgen receptor (AR) target genes, master regulators of neuroendocrine differentiation, and previously validated AR activity and treatment-associated small cell neuroendocrine carcinoma (t-SCNC) transcriptional signature scores using Pearson correlations. Associations between FOLH1 and both PSA50 response to subsequent AR-targeted therapy and overall survival (OS) were examined by logistic regression and Cox proportional hazard models, respectively. Results: Samples from 97 pts were identified, of which 18% harbored t-SCNC histology. 45% of pts had visceral metastases at the time of biopsy, and 41% received subsequent AR-targeted therapy. Median FOLH1 expression was lower in pts with visceral metastases vs no visceral metastases (14.7 vs 15.6, p = 0.02) but was not significantly different across t-SCNC vs adenocarcinoma biopsies (14.3 vs 15.4, p = 0.13). FOLH1 expression was positively correlated with AR transcriptional activity and AR target genes, and negatively correlated with master regulators of neuroendocrine differentiation and t-SCNC transcriptional signature scores (Table). Low FOLH1 expression did not predict PSA50 response to subsequent AR-targeted therapy (OR 0.97, p = 0.8), but was associated with shorter OS on univariate analysis (HR 1.09, 95% CI 1.02-1.16, p=0.01). A post-hoc analysis revealed a trend towards decreased median OS in pts with FOLH1 expression &lt;12 (7.5 vs 17.1 months, log-rank p = 0.06). Conclusions: In this retrospective analysis of mCRPC pts, low FOLH1 expression was associated with transcriptional features of t-SCNC, decreased AR activity, and shorter OS. These findings are hypothesis-generating and prospective validation is needed.[Table: see text]

Frequency and intensity of [18F]-PSMA-1007 uptake after COVID-19 vaccination in clinical PET.

Objectives:To assess the frequency and intensity of [18F]-prostate-specific membrane antigen (PSMA)-1007 axillary uptake in lymph nodes ipsilateral to COVID-19 vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) in patients with prostate cancer referred for oncological [18F]-PSMA positron emission tomography (PET)/CT or PET/MR imaging.Methods:126 patients undergoing [18F]-PSMA PET/CT or PET/MR imaging were retrospectively included. [18F]-PSMA activity (maximum standardized uptake value) of ipsilateral axillary lymph nodes was measured and compared with the non-vaccinated contralateral side and with a non-vaccinated negative control group. [18F]-PSMA active lymph node metastases were measured to serve as quantitative reference.Results:There was a significant difference in maximum standardized uptake value in ipsilateral and compared to contralateral axillary lymph nodes in the vaccination group (n = 63, p < 0.001) and no such difference in the non-vaccinated control group (n = 63, p = 0.379). Vaccinated patients showed mildly increased axillary lymph node [18F]-PSMA uptake as compared to non-vaccinated patients (p = 0.03). [18F]-PSMA activity of of lymph node metastases was significantly higher (p < 0.001) compared to axillary lymph nodes of vaccinated patients.Conclusion:Our data suggest mildly increased [18F]-PSMA uptake after COVID-19 vaccination in ipsilateral axillary lymph nodes. However, given the significantly higher [18F]-PSMA uptake of prostatic lymph node metastases compared to “reactive” nodes after COVID-19 vaccination, no therapeutic and diagnostic dilemma is to be expected.Advances in knowledge:No specific preparations or precautions (e.g. adaption of vaccination scheduling) need to be undertaken in patients undergoing [18F]-PSMA PET imaging after COVID-19 vaccination.

Impact of the molar activity and PSMA expression level on [18F]AlF-PSMA-11 uptake in prostate cancer

This two-part preclinical study aims to evaluate prostate specific membrane antigen (PSMA) as a valuable target for expression-based imaging applications and to determine changes in target binding in function of varying apparent molar activities (MAapp) of [18F]AlF-PSMA-11. For the evaluation of PSMA expression levels, male NOD/SCID mice bearing prostate cancer (PCa) xenografts of C4-2 (PSMA+++), 22Rv1 (PSMA+) and PC-3 (PSMA−) were administered [18F]AlF-PSMA-11 with a medium MAapp (20.24 ± 3.22 MBq/nmol). SUVmean and SUVmax values were respectively 3.22 and 3.17 times higher for the high versus low PSMA expressing tumors (p < 0.0001). To evaluate the effect of varying MAapp, C4-2 and 22Rv1 xenograft bearing mice underwent additional [18F]AlF-PSMA-11 imaging with a high (211.2 ± 38.9 MBq/nmol) and/or low MAapp (1.92 ± 0.27 MBq/nmol). SUV values showed a significantly increasing trend with higher MAapp. Significant changes were found for SUVmean and SUVmax between the high versus low MAapp and medium versus low MAapp (both p < 0.05), but not between the high versus medium MAapp (p = 0.055 and 0.25, respectively). The effect of varying MAapp was more pronounced in low expressing tumors and PSMA expressing tissues (e.g. salivary glands and kidneys). Overall, administration of a high MAapp increases the detection of low expression tumors while also increasing uptake in PSMA expressing tissues, possibly leading to false positive findings. In radioligand therapy, a medium MAapp could reduce radiation exposure to dose-limiting organs with only limited effect on radionuclide accumulation in the tumor.

Prostate-Specific Membrane Antigen in Anaplastic and Poorly Differentiated Thyroid Cancer-A New Diagnostic and Therapeutic Target?

Simple SummaryProstate-specific membrane antigen (PSMA)-targeted therapy represents a promising therapeutic option for the treatment of advanced carcinoma, but data on the relevance of PSMA-targeted diagnostics and therapy for anaplastic (ATC) and poorly differentiated (PDTC) thyroid carcinoma are still lacking. Due to the limited therapeutic options for these entities, the aim of this study was to evaluate to what extent Gallium-68 (68Ga)-PSMA-positron emission tomography/computed tomography (PET/CT) is superior to F-18-Fluordeoxyglucose (18F-FDG)-PET/CT in the diagnostic of ATC/PDTC and could represent a new therapeutic option in terms of theranostic. The findings of this study confirm the high diagnostic sensitivity and superiority of 18F-FDG-PET/CT in comparison to 68Ga-PSMA-PET/CT in the diagnosis of ATC and PDTC. However, it can be suggested that 68Ga-PMSA-PET/CT can be considered as a beneficial adjunct to the well-established 18F-FDG-PET/CT for a few individual selected patients with ATC and PDTC to detect lesions not discovered by 18F-FDG-PET/CT and to determine patients’ eligibility for a radioligand therapy. With regard to our results, radiolabelled PSMA-ligands with Lutetium-177 (177Lu)-PSMA may, in the future, represent a theranostic approach with only minor side effects for a few individual selected patients with ATC and PDTC who need alternative treatment options in case of progression when established therapies are no longer effective.Several studies have demonstrated an expression of the prostate-specific membrane antigen (PSMA) in the cancer-related neovasculature of thyroid malignancies. Due to the poor prognosis and limited therapeutic options for patients with anaplastic (ATC) and poorly differentiated (PDTC) thyroid carcinoma, the aim of our study was to investigate the theranostic approach of PSMA expression in these patients. The PSMA uptake on Gallium-68 (68Ga)-PSMA-positron emission tomography/computed tomography (PET/CT) and glucose uptake on F-18-Fluordeoxyglucose (18F-FDG)-PET/CTs were analysed in two ATC and six PDTC patients. The PSMA expression in corresponding patients’ tissue samples was detected by immunohistochemistry. In addition, various tissue sections from 22 ATC and six PDTC patients were examined concerning PSMA expression. 68Ga-PSMA-PET/CT showed heterogeneous PSMA expression among patients and lesions. Six of the eight analyzed patients (two ATC, four PDTC) showed increased glucose metabolism without increased PSMA uptake after PET/CT. In one patient (PDTC), 18F-FDG-PET/CT tracer uptake was positive and 68Ga-PSMA-PET/CT showed heterogeneous results. Another patient (PDTC) evidenced only PSMA-positive lesions and received two cycles of Lutetium-177 (177Lu)-PSMA therapy, which kept his disease stable for seven months. There was a correlation between immunohistochemical PSMA expression and uptake on 68Ga-PMSA-PET/CT in three of the examined patients. Twenty-seven of the analyzed 39 ATC and 13 of the analyzed 22 PDTC tissue sections showed a strong PSMA expression. Considering the rarity of PDTC and ATC, which is the reason for the small patient population we studied, the findings of this study confirm the high diagnostic sensitivity and superiority of 18F-FDG-PET/CT in comparison to 68Ga-PSMA-PET/CT in the diagnosis of ATC and PDTC. However, it can be suggested that 68Ga-PMSA-PET/CT can be considered as a beneficial adjunct to the well-established 18F-FDG-PET/CT for a few individual selected patients with ATC and PDTC to detect lesions not discovered by 18F-FDG-PET/CT and to determine patients’ eligibility for a radioligand therapy. Radiolabelled PSMA-ligands may, in the future, represent a theranostic approach with only minor side effects for a few individual selected patients with ATC and PDTC who need alternative treatment options in case of progression when established therapies are no longer effective. However, due to the small sample size of our collective, larger studies are needed to allow for a final evaluation on the significance of PSMA-targeted diagnostic and therapy for ATC and PDTC.

MP11-14 VERY LOW PROSTATE PET CT PSMA EXPRESSION MAY BE MISLEADING IN STAGING PROSTATECTOMY CANDIDATES

You have accessJournal of UrologyProstate Cancer: Staging (MP11)1 Sep 2021MP11-14 VERY LOW PROSTATE PET CT PSMA EXPRESSION MAY BE MISLEADING IN STAGING PROSTATECTOMY CANDIDATES Rennen Haramaty, Alon Lazarovich, Asaf Shvero, Miki Haifler, Jonathan Gal, Shay Golan, Sagi Shpitzer, Azik Hoffman, Omri Nativ, Yuval Freifeld, Rani Zreik, Zohar Dotan, and Barak Rosenzweig Rennen HaramatyRennen Haramaty More articles by this author , Alon LazarovichAlon Lazarovich More articles by this author , Asaf ShveroAsaf Shvero More articles by this author , Miki HaiflerMiki Haifler More articles by this author , Jonathan GalJonathan Gal More articles by this author , Shay GolanShay Golan More articles by this author , Sagi ShpitzerSagi Shpitzer More articles by this author , Azik HoffmanAzik Hoffman More articles by this author , Omri NativOmri Nativ More articles by this author , Yuval FreifeldYuval Freifeld More articles by this author , Rani ZreikRani Zreik More articles by this author , Zohar DotanZohar Dotan More articles by this author , and Barak RosenzweigBarak Rosenzweig More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001984.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 68Ga-labeled prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) computed tomography (CT) imaging quickly earns an important role in staging radical prostatectomy candidates. While PSMA is generally weakly expressed in normal prostate tissue, it is strongly upregulated in prostate cancer. However, some clinically significant prostate cancers exemplify low reads on PSMA PET CT. In the current work we evaluate this unique sub-population of patients with ‘negative’ prostate PSMA PET CT reads. METHODS: We retrospectively reviewed 392 patients who underwent radical prostatectomy between September 2014 to July 2019 in 5 medical centres.Patients with pre-operative PSMA PET CT imaging were included. We collected data on baseline characteristics including demographics, comorbidities, prostate specific antigen (PSA) and rectal exam, prior biopsies, imaging results, and biopsies and radical prostatectomy histology. An index group of patients with ‘negative’ PSMA PET CT prostate read was defined as “scarce” uptake and/or numerically maximal standardized uptake value (SUVmax) below physiologic uptake. For control we used patients with PSMA PET CT prostate read defined as “intense” and/or numerically as SUVmax above physiologic uptake. RESULTS: 97 patients had PSMA PET CT imaging prior surgery, 52 (54%) of whom fitted with the index group inclusion criteria and 45 (46%) with the control group. All pre-operative characteristics did not significantly differ in-between groups except lesion size and SUVmax per PSMA PET CT (Table1). Prostatectomy specimen’s histology analysis significantly differed in-between groups, for ISUP score, seminal vesicles invasion, T stage and positive margins rates (p<0.05).Nonetheless, 50 (96%) of the index group patients harbored clinically significant disease (ISUP>=2) with extra-prostatic disease showed in 24 (46%) and peri-neural invasion in 35 (67%).Positive lymph nodes were found in 4 (8%) of index group patients. CONCLUSIONS: While prostate cancer aggressiveness was generally correlated with intense uptake of PSMA on pre-operative PSMA/PET CT, a subpopulation of patients with clinically significant cancer and aggressive characteristics show weak reads only on this imaging. These data raise concern applying PSMA PET CT for staging of prostatectomy candidates. Source of Funding:- © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e184-e184 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rennen Haramaty More articles by this author Alon Lazarovich More articles by this author Asaf Shvero More articles by this author Miki Haifler More articles by this author Jonathan Gal More articles by this author Shay Golan More articles by this author Sagi Shpitzer More articles by this author Azik Hoffman More articles by this author Omri Nativ More articles by this author Yuval Freifeld More articles by this author Rani Zreik More articles by this author Zohar Dotan More articles by this author Barak Rosenzweig More articles by this author Expand All Advertisement Loading ...

Prostate-specific membrane antigen (PSMA)-based imaging in localized and advanced prostate cancer: a narrative review.

Combined molecular and morphologic imaging modalities have emerged in recent years as an alternative to conventional imaging in prostate cancer (PC). In particular, novel prostate-specific membrane antigen (PSMA) radiotracers have demonstrated increased sensitivity and specificity for the initial staging of men with clinically localized PC, as well as for PC detection in the setting of biochemical recurrence (BCR). Molecular imaging is increasingly used to guide treatment decisions in these patients—though its impact on survival has yet to be established. Improved PC detection in men with BCR has also helped to identify a subset of patients with oligometastatic disease. The optimal management of oligometastatic PC and the role of metastasis-directed therapies (MDT) are the subjects of ongoing studies. In comparison to clinically localized or biochemically recurrent PC, the role of molecular imaging in men with advanced disease is less established. In metastatic castration-resistant PC (mCRPC), PSMA-based imaging has primarily been investigated as a companion diagnostic tool to predict and monitor response to PSMA-targeted radioligand therapy (RLT). More recent efforts have focused on using molecular imaging to monitor treatment response to conventional chemohormonal therapies. However, despite promising early results, several barriers remain to the widespread use of PSMA-based imaging in metastatic PC: temporary flares in PSMA uptake have been described in a subset of patients after initiation of therapy, and the underlying mechanism and clinical implications of this phenomenon are still poorly understood. Furthermore, whereas PSMA is invariably expressed in hormone-sensitive PC, loss of PSMA expression is increasingly recognized in a subset of mCRPC patients with aggressive disease. Although this may limit the use of PSMA-based imaging as a standalone modality in advanced PC, loss of PSMA uptake may also provide non-invasive and clinically relevant molecular insight on patients’ underlying tumor biology.

64Cu-PSMA-BCH: a new radiotracer for delayed PET imaging of prostate cancer.

Develop a 64Cu labeled radiopharmaceutical targeting prostate specific membrane antigen (PSMA) and investigate its application for prostate cancer imaging. 64Cu-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. 64Cu-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 1h). It accumulated in 22Rv1 tumor with increasing radioactivity uptake and T/N ratios from 1 to 24h post-injection. In patients with suspected prostate cancer, SUVmax and T/N ratios increased within 24h post-injection. Compared with image at 1h post-injection, more tumor lesions were detected at 6h and 24h 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 0.0292mSv/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. 64Cu-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.

Prostate-Specific Membrane Antigen Expression in Patients With Differentiated Thyroid Cancer With Thyroglobulin Elevation and Negative Iodine Scintigraphy Using 68Ga-PSMA-HBED-CC PET/CT.

Prostate-specific membrane antigen (PSMA) is a member of superfamily of zinc-dependent exopeptidases that is robustly expressed in prostate cancer cells and nonprostatic solid tumor neovasculature including microvessels of thyroid tumors. Its expression in differentiated thyroid cancer (DTC) has been confirmed in many recent studies, but systematic studies exploring PSMA expression in patients with DTC with thyroglobulin elevation and negative iodine scintigraphy (TENIS) are lacking. The aim of the present study was to evaluate the role of PSMA scan in TENIS patients with DTC. Nine consecutive patients with DTC with proven TENIS syndrome (6 men and 3 women with age range 29-68 years and mean age of 48 years) underwent 18F-FDG PET/CT as per the institution protocol. Thereafter, they were subjected to 68Ga-PSMA-HBED-CC PET/CT as per the institution protocol within a week of FDG PET imaging. Prostate-specific membrane antigen expression (SUVmax) in the lesions was compared with 18F-FDG PET and CT scan findings. In 5 of 9 patients with TENIS, the metastatic lesions showed PSMA expression. A total of 14 lesions were seen on the CT scan. Prostate-specific membrane antigen PET detected 9 of 14 lesions (64.28%) (SUVmax ranging from 10.1 to 45.67; median SUVmax of 16.31), whereas FDG PET was positive in 11 of 14 lesions (78.57%). The lesions that showed PSMA uptake was localized to bones (5 of 9) and lungs (4 of 9). Two lesions that were localized to iliac crest and acetabulum were missed on FDG PET but were seen on CT and PSMA PET scan. The results of this pilot study indicate that 68Ga-HBED-CC-PSMA PET/CT demonstrates PSMA expression in TENIS patients with lesions being localized to the bones and lungs. 68Ga-PSMA PET/CT could be useful for the identification of TENIS patients who might benefit from PSMA-targeted radionuclide therapy.

Physiological PSMA Uptake in the Tubarial Salivary Glands and Its Implications in the PARIS Protocol-A First Study of Its Kind!

Because prostate-specific membrane antigen (PSMA) expression is universal in juvenile nasal angiofibroma (JNA), PSMA PET/CT is commonly used in the postoperative setting using the postoperative angiofibroma radionuclide imaging study protocol. Our study aims to illustrate physiological PSMA ligand uptake distribution characteristics in the salivary glands, specifically the tubarial glands with tumor, to aid in accurate PSMA PET/CT analysis. Forty-three consecutive patients who underwent a dedicated head and neck spot PSMA PET/CT for JNA were evaluated retrospectively. PSMA SUVmax values in the tumor, tubarial, parotid, submandibular, and sublingual salivary glands were determined visually and quantitatively. All the tumors and the salivary glands showed increased tracer uptake. The median SUVmax ± SD ratios of the tumor, right and left tubarial gland, right and left parotid gland, right and left submandibular gland, and right and left sublingual gland were 2.7 ± 0.8 (range, 0.5-7.5), 3.8 ± 1.9 (range, 0.9-8.1), 4.7 ± 2.1 (range, 0.8-7.4), 9.5 ± 4.8 (range, 3.2-21.9), 9.2 ± 4.7 (range, 2.9-18.9), 10.4 ± 5.7 (range, 3.5-25.4), 10.4 ± 5.5 (range, 3.7-26.4), 6 ± 4.1 (range, 1.3-20.6), and 6.5 ± 4.2 (range, 1.8-19.7), respectively. The uptake in the tubarial glands was comparable with that of the tumor but less compared with other major salivary glands. Ours is the first study demonstrating the quantitative uptake of tubarial salivary glands in detail. Because the tubarial glands uptake and the anatomical location are similar to that of the tumor, these physiological uptakes must be borne in mind to circumvent false-positive interpretations and care must be given during the planning of stereotactic radiotherapy for JNAs.

Muscarinic inhibition of salivary glands with glycopyrronium bromide does not reduce the uptake of PSMA-ligands or radioiodine

RationaleSalivary glands are highly perfused and express the prostate-specific membrane antigen (PSMA) receptor as well as the sodium—iodide symporter. As a consequence, treatment with 177Lu/225Ac-PSMA for prostate cancer or 131I for thyroid cancer leads to a high radiation dose in the salivary glands, and patients can be confronted with persistent xerostomia and reduced quality of life. Salivation can be inhibited using an antimuscarinic pharmaceutical, such as glycopyrronium bromide (GPB), which may also reduce perfusion. The primary objective of this work was to determine if inhibition with GPB could provide a considerable (> 30%) reduction in the accumulation of administered 123I or 68Ga-PSMA-11 in salivary glands.MethodsTen patients who already received a whole-body 68Ga-PSMA-11 PET/CT scan for (re)staging of prostate cancer underwent a repeat PET/CT scan with tracer administration at 90 min after intravenous injection of 0.2 mg GPB. Four patients in follow-up after thyroid cancer, who had been treated with one round of ablative 131I therapy with curative intent and had no signs of recurrence, received 123I planar scintigraphy at 4 h after tracer administration without GPB and a repeated scan at least one week later, with tracer administration at 30 min after intramuscular injection of 0.4 mg GPB. Tracer uptake in the salivary glands was quantified on PET and scintigraphy, respectively, and values with and without GPB were compared.ResultsNo significant difference in PSMA uptake in the salivary glands was seen without or with GPB (Mean SULmean parotid glands control 5.57, intervention 5.72, p = 0.50. Mean SULmean submandibular glands control 6.25, intervention 5.89, p = 0.12). Three out of 4 patients showed increased 123I uptake in the salivary glands after GPB (Mean counts per pixel control 8.60, intervention 11.46).ConclusionMuscarinic inhibition of salivation with GPB did not significantly reduce the uptake of PSMA-ligands or radioiodine in salivary glands, and can be dismissed as a potential strategy to reduce toxicity from radionuclide therapies.

68Ga-PSMA expression changes on PET/CT for response assessment during taxane-based chemotherapy in metastatic prostate cancer patients.

35 Background: Imaging-based response to systemic therapies in metastatic prostate cancer is still challenging. The aim of this study was to retrospectively investigate the association between Prostate-Specific Membrane Antigen (PSMA) expression changes on 68Ga PSMA PET/CT and the response to treatment following the start of taxane-based chemotherapies (docetaxel or cabazitaxel) in both metastatic hormonosensitive (mHSPC) and castration-resistant prostate cancer (mCRPC) patients. Methods: We retrospectively reviewed all 68Ga-PSMA-11 PET/CT scans performed at our institution from November 2014 to June 2020. We included mHSPC and mCRPC patients with a baseline 68Ga-PSMA PET/CT performed &lt; 2 months before, and a second 68Ga-PSMA PET/CT performed &lt; 3 months after docetaxel or cabazitaxel (with no modification in therapy between scans). The biological data was used to distinguish PSA-non-responders (increasing PSA or decreasing PSA by &lt; 50% from pretherapy level) and PSA-responders (decreasing PSA &gt; 50% following the start of therapy or the peak thereafter). The PSMA PET/CT response was assessed visually by two independent nuclear medicine physicians blinded to clinical data and patient outcomes. Patients were classified as PSMA-non-responders (≥1 new PSMA-expressing metastases, majority of PSMA-expressing metastases increasing in intensity, or stable PSMA-expression of the disease) or PSMA-responders (complete disappearance of pathologic PSMA uptake, or majority of PSMA-expressing metastases decreasing in intensity). Majority of lesions was defined as &gt; 50% of registered lesions. Descriptive statistics and measures of associations (two-sided Fisher’s exact test and Phi coefficient) were calculated. Results: A total of 37 patients were included (8 mHSPC and 29 mCRPC), 21 patients under docetaxel and 16 cabazitaxel. All patients received at least 3 cycles [median 6 (range 3-10)]. The mean time (±standard deviation) between the first 68Ga-PSMA PET/CT and the start of therapy was 22±16 days. The mean time between the the last cycleand the second 68Ga-PSMA PET/CT was 36±27 days. PSA-response and PSMA-response were concordant in 95% of cases with 18 patients PSA/PSMA-non-responders and 17 PSA/PSMA-responders (Phi = 0.90, p = 0.0001). Two discordant patients presented with PSMA-response but PSA-non-response. No isolated PSMA flare was observed, as PSA-response was always associated with a decrease in PSMA-expression on the second PET/CT. Conclusions: This retrospective study suggests PSMA expression changes on PET/CT at least after 3 cycles of chemotherapy (docetaxel or cabazitaxel) are strongly associated with PSA response. No flare phenomenon was found at this evaluation. Prospective studies are needed to better define the potential role of PSMA-PET/CT in response assessment.