Positive Prostate-specific Membrane Antigen Research Articles

Radical Prostatectomy Without Prior Biopsy in Selected Patients Evaluated by 18F-Labeled Prostate-Specific Membrane Antigen-Ligand Positron Emission Tomography/Computed Tomography and Multiparameter Magnetic Resonance Imaging: A Single-Center, Prospective, Single-Arm Trial.

This study aimed to verify the feasibility and short-term prognosis of prostatectomy without biopsy. Patients with a rising PSA level ranging from 4 to 30 ng/mL were scheduled for multiparametric (mp) MRI and 18F-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Forty-seven patients (cT2N0M0) with Prostate Imaging Reporting and Data System ≥ 4 and molecular imaging PSMA score ≥ 2 were enrolled. All candidates underwent robot-assisted laparoscopic radical prostatectomy without biopsy. Prostate cancer detection rate, index tumors localization correspondence rate, positive surgical margin, complications, postoperative hospital stay, and PSA level in a 6-week postoperative follow-up visit were collected. All the patients with positive mpMRI and PSMA PET were diagnosed with clinically significant prostate cancer. A total of 80 lesions were verified as cancer by pathology, of which 63 cancer lesions were clinically significant prostate cancer. Fifty-one lesions were simultaneously found by mpMRI and PSMA PET. A total of 23 lesions were invisible on either image, and all lesions were ≤ International Society of Urological Pathology 2 or ≤ 15 mm. Forty-five (95.7%) index tumors found by mpMRI combined with PSMA PET were consistent with pathology. Nine patients reported positive surgical margin. Biopsy-free prostatectomy is safe and feasible for patients with evaluation strictly by mpMRI combined with 18F-PSMA PET/CT.

PSMA PET Guided Salvage Radiotherapy Among Prostate Cancer Patients in the Post-Prostatectomy Setting: A Single Center Post-Hoc Analysis.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) shows improved sensitivity and specificity for detection of locoregional and distant metastatic prostate cancer (PCa) compared to conventional imaging, especially at lower PSA levels as is often the case in the biochemically recurrent (BCR), post radical prostatectomy (RP) setting. Providers are now utilizing PSMA PET findings to guide their salvage radiotherapy (sRT) treatment fields and doses, although it is not well understood how PSMA PET guided sRT impacts patient outcomes. This was a post-hoc analysis of 5 prospective studies of PSMA PET conducted at UCLA from 2016 to 2021 that included patients with recurrent PCa following RP. Patients were included in this retrospective study if they initiated sRT within 3 months of PSMA PET, had at least 12 months of follow up after sRT completion, had available sRT treatment details, and did not have distant metastases (DM) by conventional imaging on upfront staging. Patients treated with palliative RT were excluded. BCR following sRT was defined as an increase in PSA of 0.2 ng/ml above the post sRT nadir. Metastasis directed therapy (MDT) was defined as sRT to all PSMA+ N1 and M1 lesions. Baseline patient demographics, PSMA PET findings, sRT & ADT treatment details, and patient outcome data were collected. A total of 176 patients were included in this study. Median time between RP and PSMA PET was 38 months (range 1-329). Median PSA at the time of the PSMA PET was 0.625 ng/mL (range 0.063-35). PSMA PET was positive in 128 patients (73%): 21 (12%) miT+N0M0, 55 (31%) miTxN1M0 and 52 (30%) miTxNxM1 with 19 (11%) miTxNxM1a, 31 (18%) miTxNxM1b, and 2 (1%) miTxNxM1c. Median number of lesions seen on positive PSMA scans was 1 (range 1-8). 39 (22%) patients were subsequently treated with sRT to the prostate bed (PB) only, 59 (34%) to PB + pelvic lymph nodes (PLNs), 33 (19%) to PLNs only, 7 (4%) to PB + PLNs + DM, 7 (4%) to PLNs + DM, and 31 (18%) to DM only. 59 (34%) patients were treated with concurrent ADT at a median duration of 6 months (range 1-39). At a median follow-up of 32 months (range 12-70) after sRT, 80 patients (45%) did not develop BCR or imaging relapse (IR) following sRT, 24 patients (14%) developed BCR but not IR, 1 patient (<1%) developed IR only, and 70 patients (40%) developed both BCR and IR. The median time to BCR and IR following sRT was 15 months (range 1-48) and 19 months (range 6-61), respectively. 1 year post sRT biochemical recurrence free survival was 77%. Of the 83 patients treated with MDT, 32 (39%) did not develop subsequent disease relapse. This post hoc analysis assessed the outcomes of 176 patients treated with PSMA PET guided salvage RT, proving it to be an effective method for treating both pelvic and extrapelvic recurrent PCa. Further investigation is needed to assess the full extent of patient outcomes in this population.

Prostate-specific membrane antigen positron emission tomography detected local failure after post-prostatectomy radiation therapy: Low rates of out-of-field recurrence validates current Australian prostate bed contouring guidelines.

The Australian Faculty of Radiation Oncology Genitourinary Group (FROGG) developed prostate bed clinical target volume (CTV) contouring guidelines which were subsequently used to develop the National EviQ guidelines for adjuvant and salvage post-prostatectomy radiotherapy (PPRT). These guidelines were based mainly upon consensus agreement. With the advent of prostate-specific membrane antigen (PSMA) positron emission tomography (PET), sites of recurrence can now be detected with low prostate-specific antigen (PSA) levels following radical prostatectomy. We evaluated sites of recurrence in patients treated with FROGG/EviQ CTVs to inform upcoming modifications of these guidelines. At our institution, we use the FROGG/EviQ guidelines for PPRT. From 2015, patients with PSA failure following PPRT have been re-staged using PSMA PET imaging. We identified patients with PET-avid local, nodal, and distant recurrences, fusing them with original treatment plans to determine whether recurrences were within or outside the prostate bed CTV. Regional nodal failures were reviewed to determine if they were within current elective node contouring guidelines. Ninety-four patients had positive PSMA PET following PPRT. Nine (9.6%) recurrences were local, seven being local-only. One local recurrence (1.1%) was just superior to the contoured prostate bed CTV, located within the vas deferens. Seventy-three (77.7%) patients had a component of node failure, with 56 (59.6%) having node-only failure. Sites of nodal relapses were covered by standard contouring guidelines 60.3% of the time. The low recurrence rate outside of current prostate bed CTV contouring guidelines is consistent with other studies using contemporary contouring, and validates the efficacy of the current FROGG/EviQ prostate bed CTV definition.

Retrospective review of 250 gallium-68 PSMA scans in prostate cancer patients in Health Canada Special Access Program.

e17035 Background: Prostate Cancer is the most common malignancy in men, and until recently has been staged using standard imaging tests, such as ultrasound, CT, bone scan, and MRI. A novel imaging test targeting the membrane receptor, Prostate Specific Membrane Antigen (PSMA) using the PET tracer Ga-68 PSMA-11 has recently been approved in several countries for staging and assessing potential for radionuclide therapy. This agent was only recently approved in Canada, but has been available through the Health Canada Special Access (SA) Program for over a year, until it was approved (Illuccix, Telix Pharmaceuticals). Methods: In the past year, 275 prostate cancer patients were scanned at our facility (INITIO Medical Imaging, Burnaby BC) through Health Canada SA. All patients were required to have positive prostate cancer biopsies, with negative or indeterminate CT and bone scan, and rising PSA (prostate specific antigen) blood test in order to qualify for SA, or high risk Gleason Score prostate cancer. Results: Of the 275 patients, 71 had high risk cancers and 28/71 had positive PSMA studies (39%). 185 of the patients had biochemical evidence of recurrence and negative /indeterminate conventional imaging tests, and 101/185 or 55% had positive PSMA scans. All other patients were scanned for metastatic castrate resistant prostate cancer (MCRPC). Conclusions: Ga-68 PSMA scans are highly sensitive for upstaging patients at high risk of prostate cancer metastasis or recurrence, even with negative conventional imaging studies.

PSMA PET guided salvage radiotherapy among patients with prostate cancer in the post-prostatectomy setting: A single center post-hoc analysis.

5009 Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) shows improved sensitivity and specificity for detection of locoregional and distant metastatic prostate cancer (PCa) compared to conventional imaging, especially at lower PSA levels as is often the case in the biochemically recurrent (BCR), post radical prostatectomy (RP) setting. Providers are now utilizing PSMA PET findings to guide their salvage radiotherapy (sRT) treatment fields and doses, although it is not well understood how PSMA PET guided sRT impacts patient outcomes. Methods: This was a post-hoc analysis of 5 prospective studies of PSMA PET conducted at UCLA from 2016 to 2021 that included patients with recurrent PCa following RP. Patients were included in this retrospective study if they initiated sRT within 3 months of PSMA PET, had at least 12 months of follow up after sRT completion, had available sRT treatment details, and did not have distant metastases (DM) by conventional imaging on upfront staging. Patients treated with palliative RT were excluded. BCR following sRT was defined as an increase in PSA of 0.2 ng/ml above the post sRT nadir. Metastasis directed therapy (MDT) was defined as sRT to all PSMA+ N1 and M1 lesions. Baseline patient demographics, PSMA PET findings, sRT &amp; ADT treatment details, and patient outcome data were collected. Results: 176 patients were included in this study. Median time between RP and PSMA PET was 38 months (range 1-329). Median PSA at the time of the PSMA PET was 0.625 ng/mL (range 0.063-35). PSMA PET was positive in 128 patients (73%): 21 (12%) miT+N0M0, 55 (31%) miTxN1M0 and 52 (30%) miTxNxM1 with 19 (11%) miTxNxM1a, 31 (18%) miTxNxM1b, and 2 (1%) miTxNxM1c. Median number of lesions seen on positive PSMA scans was 1 (range 1-8). 39 (22%) patients were subsequently treated with sRT to the prostate bed (PB) only, 59 (34%) to PB + pelvic lymph nodes (PLNs), 33 (19%) to PLNs only, 7 (4%) to PB + PLNs + DM, 7 (4%) to PLNs + DM, and 31 (18%) to DM only. 59 (34%) patients were treated with concurrent ADT at a median duration of 6 months (range 1-39). At a median follow-up of 32 months (range 12-70) after sRT, 80 patients (45%) did not develop BCR or imaging relapse (IR) following sRT, 24 patients (14%) developed BCR but not IR, 1 patient (&lt;1%) developed IR only, and 70 patients (40%) developed both BCR and IR. The median time to BCR and IR following sRT was 15 months (range 1-48) and 19 months (range 6-61), respectively. 1 year post sRT biochemical recurrence free survival was 77%. Of the 83 patients treated with MDT, 32 (39%) did not develop subsequent disease relapse. Conclusions: This post-hoc analysis assessed the outcomes of 176 patients treated with PSMA PET guided salvage RT, proving it to be an effective method for treating both pelvic and extrapelvic recurrent PCa. Further investigation is needed to assess the full extent of patient outcomes in this population.

Prostate-Specific Membrane Antigen (PSMA) Expression in The Neovasculature of High Grade Gliomas (Histopathological and Immunohistochemical Study).

Prostate-specific membrane antigen (PSMA) was first noticed in prostate cancer cells, thereafter, It has been found in the endothelial cells of neovasculature in a variety of tumors, but not in normal vascular endothelium, This specificity makes PSMA an ideal molecule for vascular targeting in Cancer theranostics (i.e., combined diagnostic and therapeutic). The objective of this study was to evaluate the immunohistochemical (IHC) expression of PSMA in the neovasculature (identified by CD 31) of high-grade gliomas (HGGs) and to Correlate PSMA IHC expression in HGGs with clinicopathological features, to detect its possible role in tumor angiogenesis, where PSMA can be used as a future diagnostic and therapeutic target. This retrospective study included a total of 69 archived, formalin-fixed, paraffin-embedded tissue blocks of HGGs, including 52 cases classified as WHO grade IV (75.4%) and 17 cases as WHO grade III (24.6%). The samples were immunohistochemically analyzed for PSMA expression (in both TMV and parenchymal tumor cells) which was assessed using the composite PSMA immunostaining score. A score (0) was considered negative while scores 1-7 were considered positive (1-4, 5-6, or 7; weak, moderate, or strong respectively). PSMA is expressed specifically and significantly in endothelial cells of tumor microvessels (TMV) of HGGs, A statistically significant relationship was detected between PSMA IHC expression in both TMV and in parenchymal tumor cells (TC) and various glioma subtypes (P-value < 0.05 and <0.001 respectively). Positive PSMA immunostaining in TMV was detected in all anaplastic ependymoma cases and in near all cases of classic GB and GB with oligodendroglial features more than other subtypes, with P-value specifically for PSMA positivity/negativity in TMV statistically significant (0.022). While for Tumor cells, Positive PSMA immunostaining was detected in all anaplastic ependymoma, most anaplastic astrocytoma and classic GB cases in contrary to other variants, with P-value statistically extremely significant (< 0.001). Comparing PSMA IHC expression in TMV and its expression in TC, it was significantly expressed in TMV of 82.7% versus TC of 51.9% of grade IV cases. Likewise, in GB with oligodendroglial features and gliosarcoma, the majority of cases showed positive staining in their TMV [8/8 (100%), 9/13 (69.2%) respectively], and, the reverse occurs in tumor cells where the majority of cases did NOT show staining in the tumor cells for PSMA (5/8 (62.5%), 11/13 (84.6%) of cases respectively), which was statistically significant (P-value ≤ 0.05) besides the significant difference in the pattern of staining according to composite PSMA scoring (P-value ≤ 0.05). PSMA has a possible role in tumor angiogenesis, therefore it might be considered a potential promising endothelial target for Cancer theranostics with PSMA-based agents, in addition, PSMA was expressed significantly in TC of HGGs, thus, it appears to be involved in biologic behavior, carcinogenesis and tumor progression.

Detection efficacy of PET/CT with 18F-FSU-880 in patients with suspected recurrent prostate cancer: a prospective single-center study.

Our objective was to investigate the efficacy of PET/CT with a novel prostate-specific membrane antigen (PSMA)-targeted PET probe, 18F-FSU-880, for detection and localization of recurrent disease in prostate cancer patients in whom recurrence was suspected based on an increase in plasma prostate-specific antigen (PSA) levels after initial treatment. This study was a prospective institutional review board-approved study of 72 patients (age 56-84years, PSA level 0.22-40.00ng/ml) with suspected relapse of prostate cancer after primary therapy, including radical prostatectomy (RP) (n = 35) or radiation therapy (RT) (n = 37). Patients underwent PET/CT approximately 1h and 3h after injection of 18F-FSU-880 (101.8-380MBq). The correlation between patient-based detection rate and Gleason score (GS) of the primary tumor and plasma PSA levels at the time of PET/CT was evaluated. Maximum standardized uptake values (SUVmax) of the positive uptakes at 1h post-injection were compared with those at 3h post-injection. In total, 51 patients (71%) showed at least one positive PSMA PET result. The PSA-stratified detection rates were 22% (2/9), 36% (4/11), 89% (16/18) and 85% (29/34) for PSA levels of 0.2 to < 0.5, 0.5 to < 1.0, 1.0 to < 2.0 and ≥ 2.0ng/ml, respectively. The GS-stratified detection rates were 33% (2/6), 67% (16/24), 70% (16/23) and 89% (17/19) for GS 6, 7, 8 and 9, respectively. In lesion-based analysis, 157 positive lesions were detected at 3h post-injection, 18 in the prostate or prostate bed, 65 in lymph nodes, 71 in the bone and 3 in the lung. Two local recurrences, eight pelvic lymph nodes and one distant lymph node were depicted only at 3h post-injection. SUV max at 3h post-injection was significantly higher than SUVmax at 1h post-injection (p < 0.001). Our preliminary data suggest that 18F-FSU-880 might be a promising new PSMA-targeting tracer for detecting recurrence after initial treatment in patients with prostate cancer.

PD61-02 PREOPERATIVE PSMA PET/CT AS A PREDICTOR OF BIOCHEMICAL PERSISTENCE AND EARLY BIOCHEMICAL RECURRENCE

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V (PD61)1 Sep 2021PD61-02 PREOPERATIVE PSMA PET/CT AS A PREDICTOR OF BIOCHEMICAL PERSISTENCE AND EARLY BIOCHEMICAL RECURRENCE Diederik Baas, Melline Schilham, Joost de Baaij, Eric Vrijhof, Robert Hoekstra, Rick Hermsen, Diederik Somford, and Jean-Paul van Basten Diederik BaasDiederik Baas More articles by this author , Melline SchilhamMelline Schilham More articles by this author , Joost de BaaijJoost de Baaij More articles by this author , Eric VrijhofEric Vrijhof More articles by this author , Robert HoekstraRobert Hoekstra More articles by this author , Rick HermsenRick Hermsen More articles by this author , Diederik SomfordDiederik Somford More articles by this author , and Jean-Paul van BastenJean-Paul van Basten More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002098.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This study aims to evaluate the predictive value of suspected lymph nodes (LN) metastases on prostate-specific-membrane-antigen (PSMA) PET/CT for biochemical persistence (BCP) and early biochemical recurrence (BCR) following radical prostatectomy (RP) with extended pelvic lymph node dissection (ePLND). METHODS: RP patients between September 1st, 2016 and October 1st, 2020 were evaluated. Men with intermediate or high-risk PCa with preoperative 68Ga/18F-PSMA PET/CT and subsequent ePLND were included. Performance of PSMA PET/CT was determined on a per patient level. BCP was defined as a serum PSA level ≥0.1 ng/mL between 6-20 weeks following RP. Early BCR was defined as detectable PSA >0.2 ng/mL ≤12 months of follow-up. Patients were grouped as PSMA- or PSMA+ depending on their LN status on PSMA PET/CT and subdivided according to histological LN status (pN) as determined by ePLND. RESULTS: From 1058 consecutive RP patients, 213 met the inclusion criteria. Median number of resected LN was 20 (IQR 15-26). PSMA PET/CT versus histological results of ePLND are presented in Table 1. Sensitivity, specificity, PPV, NPV and accuracy for preoperative detection of metastatic LNs were 29%, 83%, 33%, 80% and 71% respectively. BCP was observed in 26 of 211 patients (12%) and early BCR in 23 of 110 patients (21%). The incidence of BCP and BCR for patients subdivided according to their PSMA and pN status is illustrated in Figure 1. No correction was made for other risk factors. Patients with PSMA+/pN1 had a significantly increased risk of BCP and BCR compared with PSMA-/pN1 (p=0.004; p <0.001). CONCLUSIONS: ePLND should not be avoided in men with a pre-operative negative PSMA PET/CT, as 20% of patients do have histological N1 disease. Men with positive pre-operative PSMA PET/CT and confirmed pN1 disease have a significantly increased risk of BCP and early BCR compared to those with negative PSMA PET/CT. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1066-e1066 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Diederik Baas More articles by this author Melline Schilham More articles by this author Joost de Baaij More articles by this author Eric Vrijhof More articles by this author Robert Hoekstra More articles by this author Rick Hermsen More articles by this author Diederik Somford More articles by this author Jean-Paul van Basten More articles by this author Expand All Advertisement Loading ...

Positive Multifocal PSMA PET/CT in a Patient With Prostate Cancer and Follicular Lymphoma.

Prostate-specific membrane antigen (PSMA) PET/CT is a highly reliable nuclear tracer for diagnostic imaging of prostate cancer. However, PSMA is also expressed by some nonprostatic tissues such as benign tumors, inflammatory processes, and malignant neoplasms. This case presents a patient with prostate cancer and follicular lymphoma undergoing PSMA PET/CT. Remarkably, both tumor entities were clearly detected in the scan. Yet, the 2 malignancies demonstrated rather different ranges in terms of SUVmax uptake values and therefore still enabled precise and accurate discrimination of prostate cancer and follicular lymphoma.

Diagnostic Performance and Clinical Impact of 68Ga-PSMA-11 PET/CT Imaging in Early Relapsed Prostate Cancer After Radical Therapy: A Prospective Multicenter Study (IAEA-PSMA Study).

Biochemical recurrence (BCR) is a clinical challenge in prostate cancer (PCa) patients, as recurrence localization guides subsequent therapies. The use of PET with prostate-specific membrane antigen (PSMA) provides better accuracy than conventional imaging practice. This prospective, multicenter, international study was performed to evaluate the diagnostic performance and clinical impact of PSMA PET/CT for evaluating BCR in PCa patients in a worldwide scenario. Methods: Patients were recruited from 17 centers in 15 countries. Inclusion criteria were histopathologically proven prostate adenocarcinoma, previous primary treatment, clinically established BCR, and negative conventional imaging (CT plus bone scintigraphy) and MRI results for patients with PSA levels of 4-10 ng/mL. All patients underwent PET/CT scanning with 68Ga-PSMA-11. Images and data were centrally reviewed. Multivariate logistic regression analysis was applied to identify the independent predictors of PSMA-positive results. Variables were selected for this regression model on the basis of significant associations in the univariate analysis and previous clinical knowledge: Gleason score, the PSA level at the time of the PET scan, PSA doubling time, and primary treatment strategy. All patients were monitored for a minimum of 6 mo. Results: From a total of 1,004 patients, 77.7% were treated initially with radical prostatectomy and 22.3% were treated with radiotherapy. Overall, 65.1% had positive PSMA PET/CT results. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment (P < 0.001). Treatment was modified on the basis of PSMA PET/CT results in 56.8% of patients. PSMA PET/CT positivity rates were consistent and not statistically different among countries with different incomes. Conclusion: This multicenter, international, prospective trial of PSMA PET/CT confirmed its capability for detecting local and metastatic recurrence in most PCa patients in the setting of BCR. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment. PSMA PET/CT results led to changes in therapeutic management in more than half of the cohort. The study demonstrated the reliability and worldwide feasibility of PSMA PET/CT in the workup of PCa patients with BCR.

Imaging expression of prostate‐specific membrane antigen and response to PSMA‐targeted β‐emitting radionuclide therapies in metastatic castration‐resistant prostate cancer

Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) has demonstrated efficacy and tolerability with a dose-response effect in phase I/II trials in men with metastatic castration-resistant prostate cancer (mCRPC). The need for positive PSMA imaging before PSMA-TRT to select patients is largely practiced, but its utility is not proven. Given target heterogeneity, developing a biomarker to identify the optimal patient population remains an unmet need. The aim of this study was to assess PSMA uptake by imaging and response to PSMA-TRT. We performed an analysis of men with mCRPC enrolled in sequential prospective phase I/II trials of PSMA-TRT. Each patient had baseline PSMA imaging by planar 111 In and/or 177 Lu SPECT (N = 171) or 68 Ga-PSMA-11 PET/CT (N = 44), but the results were not used to include/exclude treatment. Semiquantitative imaging scores (IS) on a 0-4 scale were assigned based on PSMA uptake in tumors compared to liver uptake. We compared the≥50% PSA decline response proportions between low (0-1) and high (2-4) PSMA IS using the χ2 -test. We used multivariable logistic regression analysis to understand the relationship between independent and dependent variables, including IS, radionuclide activity (dose) administered, CALGB (Halabi) prognostic risk score, prior taxane use. 215 men with progressive mCRPC received PSMA-TRT as follows: 177 Lu-J591 (n = 137), 177 Lu-PSMA-617 (n = 44), 90 Y-J591 (n = 28), 177 Lu-J591 + 177 Lu-PSMA-617 (n = 6). High PSMA expression (IS 2-4) was found in 160 (74.4%) patients and was significantly associated with more frequent ≥ 50% PSA reduction (26.2 vs. 7.3%, p = .006). On multivariate logistic regression analysis, higher IS was associated with a ≥50% decrease in PSA, even after accounting for CALGB (Halabi) prognostic score, the dose administered, and previous taxane use (OR, 4.72; 95% CI, 1.71-16.85; p = .006). Patients with low PSMA expression (N = 55, 24.7%) were less likely to respond. Thirteenof 26 (50%) with no PSMA uptake (IS = 0) had post-PSMA-TRT PSA decline with 2 (7.7%) having ≥ 50% PSA declines. Collectively, the data provide evidence in favor of the hypothesis that patients with high PSMA uptake and high administered radionuclide dose correlate with a higher chance of response.

18F-DCFPyL PET/CT Imaging in Patients with Biochemically Recurrent Prostate Cancer After Primary Local Therapy

Our objective was to investigate the lesion detection rate of 18F-DCFPyL PET/CT, a prostate-specific membrane antigen (PSMA)-targeted PET agent, in patients with biochemically relapsed prostate cancer after primary local therapy. Methods: This was a prospective institutional review board-approved study of 90 patients with documented biochemical recurrence (median prostate-specific antigen [PSA], 2.5 ng/mL; range, 0.21-35.5 ng/mL) and negative results on conventional imaging after primary local therapies, including radical prostatectomy (n = 38), radiation (n = 27), or a combination of the two (n = 25). Patients on androgen deprivation therapy were excluded. Patients underwent whole-body 18F-DCFPyL PET/CT (299.9 ± 15.5 MBq) at 2 h after injection. The PSMA PET lesion detection rate was correlated with PSA, PSA kinetics, and original primary tumor grade. Results: Seventy patients (77.8%) showed positive PSMA PET results, with a total of 287 lesions identified: 37 prostate bed foci, 208 lesions in lymph nodes, and 42 in distant sites in bones or organs, Eleven patients had negative results, and 9 patients showed indeterminate lesions, which were considered negative in this study. The detection rates were 47.6% (n = 10/21), 50% (n = 5/10), 88.9% (n = 8/9), and 94% (n = 47/50) for PSA levels of >0.2 to <0.5, 0.5 to <1.0, 1 to <2.0, and ≥2.0 ng/mL, respectively. In postsurgical patients, PSA, PSA doubling time, and PSA velocity correlated with PET results, but the same was not true for postradiation patients. These parameters also correlated with the extent of disease on PET (intrapelvic vs. extrapelvic). There was no significant difference in the rate of positive scans between patients with higher-grade and lower-grade primary tumors (Gleason score of ≥4 + 3 vs. <3 + 4). Tumor recurrence was histology-confirmed in 40% (28/70) of patients. On a per-patient basis, positive predictive value was 93.3% (95% confidence interval, 77.6%-99.2%) by histopathologic validation and 96.2% (95% confidence interval, 86.3%-99.7%) by the combination of histology and imaging/clinical follow-up. Conclusion: 18F-DCFPyL PET/CT imaging offers high detection rates in biochemically recurrent prostate cancer patients and is positive in about 50% of patients with a PSA level of less than 0.5 ng/mL, which could substantially impact clinical management. In postsurgical patients, 18F-DCFPyL PET/CT correlates with PSA, PSA doubling time, and PSA velocity, suggesting it may have prognostic value. 18F-DCFPyL PET/CT is highly promising for localizing sites of recurrent prostate cancer.

Prostate-Specific Membrane Antigen PET/CT Combined with Sentinel Node Biopsy for Primary Lymph Node Staging in Prostate Cancer.

Our objective was to determine the diagnostic capabilities of combined prostate-specific membrane antigen (PSMA) PET/CT and sentinel node (SN) biopsy in PSMA PET/CT-negative patients for primary lymph node (LN) staging in prostate cancer (PCa) patients. Methods: Between January 2017 and March 2019, retrospectively, all consecutive patients with diagnosed intermediate- or high-risk primary PCa who underwent preoperative PSMA PET/CT (68Ga or 18F-DCFPyL) followed by robot-assisted radical prostatectomy and extended pelvic LN dissection (ePLND) were included. All patients without suspected LN metastases on PSMA PET/CT were considered candidates for SN biopsy with indocyanine green-99mTc-nanocolloid or 99mTc-nanocolloid with free indocyanine green used as tracers. The ePLND was used as a reference standard. Results: Of 53 patients, 22 had positive PSMA PET/CT results and 31 underwent subsequent SN biopsy after negative PSMA PET/CT results. In total, 23 patients (43%) were pN1, of whom 6 (26%) had negative PSMA PET/CT results and underwent subsequent SN biopsy. The combined use of SN biopsy and PSMA PET/CT identified all pN1 patients (100% sensitivity; 95% confidence interval, 86%-100%) and performed correct nodal staging in 50 of 53 patients (94% diagnostic accuracy; 95% confidence interval, 84%-99%). SN biopsy identified significantly smaller LN metastases (median diameter, 2.0 mm; interquartile range, 1.0-3.8 mm) than PSMA PET/CT (median diameter, 5.5 mm; interquartile range, 2.6-9.3 mm; P = 0.007). Conclusion: Combining both modalities led to a 94% accuracy for nodal staging in diagnosed intermediate- and high-risk primary PCa. Adding SN biopsy in patients with negative PSMA PET/CT results increased the combined sensitivity to 100% for detecting nodal metastases at ePLND. This diagnostic accuracy may provide valuable information for directing further treatment in PCa patients, such as the use of PSMA PET/CT and SN biopsy rather than ePLND as the preferred approach for staging before radiotherapy.

Expression of Prostate-Specific Membrane Antigen (PSMA) in Brain Glioma and its Correlation with Tumor Grade

Angiogenesis is an essential component of tumor growth. Expression of PSMA on the neo-vasculature of many solid tumors, including glioblastoma multi-form, has been determined. The pattern of expression suggests that PSMA may play a functional role in angiogenesis. expression of PSMA in different grades of brain glioma was evaluated by the immunohistochemistry method to determine the probable usefulness of anti-PSMA antibody as complementary target therapy in different grades of glioma. Overall, 72 cases of low (grade I and II) and high (grade III and IV) grade gliomas were evaluated for expression of PSMA. Positive PSMA staining was observed in 12 (33.3%) of high grade and 3 (8.3%) of low grade gliomas. Although, high grade tumors more commonly had positive result for PSMA (P value=0.009), the intensity of staining was significantly stronger in low-grade tumors (P value=0.009). Expression of PSMA in different grades of glioma might provide a basis for further investigations focusing on selective target therapy in combination with the current standard care in all glioma grades, to improve treatment efficacy.

MP18-11 EXPLORING THE CLINICAL UPTAKE AND USE OF PSMA PET MRI HYBRID IMAGING IN PROSTATE CANCER PATIENTS AT AN ACADEMIC CENTER IN AUSTRALIA

You have accessJournal of UrologyImaging/Radiology: Uroradiology III1 Apr 2017MP18-11 EXPLORING THE CLINICAL UPTAKE AND USE OF PSMA PET MRI HYBRID IMAGING IN PROSTATE CANCER PATIENTS AT AN ACADEMIC CENTER IN AUSTRALIA Andre Joshi, Cheryl Nicholson, Handoo Rhee, Ian McKenzie, Janelle Munns, Greg Malone, Eric Chung, Malcolm Lawson, Peter Heathcote, John Preston, Simon Wood, Sonja Gustafson, Ken Miles, and Ian Vela Andre JoshiAndre Joshi More articles by this author , Cheryl NicholsonCheryl Nicholson More articles by this author , Handoo RheeHandoo Rhee More articles by this author , Ian McKenzieIan McKenzie More articles by this author , Janelle MunnsJanelle Munns More articles by this author , Greg MaloneGreg Malone More articles by this author , Eric ChungEric Chung More articles by this author , Malcolm LawsonMalcolm Lawson More articles by this author , Peter HeathcotePeter Heathcote More articles by this author , John PrestonJohn Preston More articles by this author , Simon WoodSimon Wood More articles by this author , Sonja GustafsonSonja Gustafson More articles by this author , Ken MilesKen Miles More articles by this author , and Ian VelaIan Vela More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.621AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Positron emission tomography (PET) using prostate specific membrane antigen (PSMA) detects prostate cancer lesions with a higher sensitivity and specificity when compared to standard imaging. Hybrid PET Magnetic Resonance Imaging (MRI) has now been introduced to provide potentially improved characterization of lesions with added PET avidity. We evaluate the utilization of this novel imaging modality at the Princess Alexandra Hospital (PAH) and assess our initial outcomes. METHODS A retrospective review of all PSMA PET MRI scans undertaken at the PAH since the introduction of the technology was performed. Imaging data was collected alongside baseline clinical data, PSA, previous histology, previous treatments, indication of scans, requesting clinicians and clinical outcomes. RESULTS A total of 187 PSMA PET MRI scans were performed at the PAH from April 2015 to October 2016. The median age of imaged patients was 68, with a median PSA of 6ng/ml and Gleason score of 7 at the time of scan. 153 scans were positive for PSMA avid disease (81.8%). Scans were requested in the setting of biochemical recurrence (n=94), preoperative staging (n=77), evaluation of treatment response (n=11) and diagnostic purposes (n=5). Urologists requested PSMA PET MRI most frequently with 111 scans, of which 58.6% requested for preoperative staging. Radiation oncologists requested 69 scans with 75.4% of these in the biochemical recurrence setting. Only 7 scans were requested by medical oncologists. Amongst patients with biochemical recurrence the lowest PSA of a positive scan was 0.02 ng/ml. In this group 43 patients had prior surgery with 19 positive scans (44%). 51 patients were treated with ADT and or EBRT and 46 had positive scans (90.2%). 29 patients had tissue samples to validate PSMA PET MRI. 26 patients (89.7%) had adenocarcinoma on histology correlating with avid lesions on PSMA PET. CONCLUSIONS PSMA PET MRI has had rapid uptake in use since introduction at the PAH. Urologists and radiation oncologists appear to utilize this imaging modality most; Urologists for a preoperative “one stop shop” staging study and radiation oncologists in biochemical recurrence. From this data is also appears that a positive PSMA PET/MRI is highly suggestive of prostate cancer, with a specificity of 89.7%. Hybrid PET/MRI may be used to stage men locally and systemically with one scan, with lower radiation and at PSA ≤1 ng/ml. This modality has the potential to significantly improve prostate cancer staging and allow early identification of recurrent disease. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e224 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Andre Joshi More articles by this author Cheryl Nicholson More articles by this author Handoo Rhee More articles by this author Ian McKenzie More articles by this author Janelle Munns More articles by this author Greg Malone More articles by this author Eric Chung More articles by this author Malcolm Lawson More articles by this author Peter Heathcote More articles by this author John Preston More articles by this author Simon Wood More articles by this author Sonja Gustafson More articles by this author Ken Miles More articles by this author Ian Vela More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Focal positive prostate-specific membrane antigen (PSMA) expression in ganglionic tissues associated with prostate neurovascular bundle: implications for novel intraoperative PSMA-based fluorescent imaging techniques

Focal positive prostate-specific membrane antigen (PSMA) expression in ganglionic tissues associated with prostate neurovascular bundle: implications for novel intraoperative PSMA-based fluorescent imaging techniques

PSMA expression is highly homogenous in primary prostate cancer.

Prostate-specific membrane antigen (PSMA) is a suggested target for antibody-based therapy of prostate cancer, potentially involved in the regulation of cell migration. As heterogeneity may limit the applicability of targeted therapies, this study was undertaken to estimate the degree of heterogeneity of PSMA expression in prostate cancer. For heterogeneity analysis, a prostate cancer heterogeneity TMA containing samples from 10 different tumor blocks of 189 consecutive prostate cancers was used. PSMA expression was analyzed by immunohistochemistry. PSMA expression was found in 97.6% of 1171 interpretable tissue spots including 260 (22.2%) with weak, 345 (29.5%) with moderate, and 538 (45.9%) with strong positivity. On a patient level, a positive PSMA immunostaining was found in 172 of 173 analyzable patients (99.4%) with at least a weak staining reaction. PSMA immunostaining was homogenously positive in 161 prostate cancers (93.6%), whereas heterogenous PSMA positivity was seen in 11 of 172 positive cases (6.4%). In these cases, heterogeneity was intrafocal in 8 cases (72.7%) and interfocal in 27.3% cases. PSMA expression was completely absent in 1 patient. Given the high frequency and high homogeneity of PSMA expression in prostate cancer, we conclude that increased PSMA expression may occur early in prostate cancer development. High homogeneity of PSMA expression is a strong argument for a high utility of PSMA as a prostate cancer drug target.

Preclinical evaluation of a bispecific low‐molecular heterodimer targeting both PSMA and GRPR for improved PET imaging and therapy of prostate cancer

It has recently been reported that metastases of prostate cancer usually show highly heterogeneous or partly lost prostate-specific membrane antigen (PSMA) expression. In order to image and treat both PSMA positive and negative tissues PSMA targeting probes need to be extended by a further specificity. Since prostate cancer cells usually express both PSMA and gastrin-releasing peptide receptor (GRPR) a bispecific low-molecular heterodimeric molecule, addressing both targets at the same time, may significantly improve prostate cancer imaging and therapy. The nonapeptide BZH3 representing the GRPR binding part was combined with the urea-based PSMA inhibitor Glu-urea-Lys(Ahx)-HBED-CC. The syntheses of the compounds were performed according to standard Fmoc-solid phase peptide synthesis. The binding properties were analyzed by competitive cell binding and internalization experiments. The in vivo targeting properties were investigated by means of biodistribution studies. Cell binding experiments revealed high binding affinities to both GRPR and PSMA expressing cell lines. The heterodimer bound with IC50 -values essentially matching the IC50 values of the respective monomers (25.0 ± 5.4 nM for PSMA and 9.0 ± 1.8 nM for GRPR, respectively). In vivo, the heterodimer showed dual targeting of PSMA (5.4%ID/g for PSMA-positive tumors) and GRPR receptors (3.3% ID/g for GRPR-positive tumors) while exhibiting fast pharmacokinetic properties. The clearance from background was comparable to the monomeric PSMA-targeting reference. The heterodimeric molecule is a promising agent for PET imaging of primary and recurrent prostate cancer covering two receptor entities which might lead to an improved diagnostic sensitivity and therapeutic efficiency.

Preparation of Asymmetric Urea Derivatives that Target Prostate-Specific Membrane Antigen for SPECT Imaging

Prostate-specific membrane antigen (PSMA) has been identified as a diagnostic and therapeutic target for prostate cancer. (S)-2-[3-[(R)-1-Carboxy-2-mercaptoethyl]ureido-pentanedioic acid (Cys-CO-Glu) were used to design novel PSMA targeting probes by nucleophilic conjugate addition between cysteine and maleimide based reagents. 3 ([(123)I]IGLCE) was synthesized by this strategy and showed high affinity for PSMA. Results of binding inhibition assays of these derivatives suggested the importance of an aromatic group and succinimide moiety for high affinity. [(123)I]3 was evaluated in vivo with PSMA positive LNCaP and PSMA negative PC-3 human prostate cancer xenograft bearing mice. [(125)I]3 accumulated in LNCaP tumors but not in PC-3 tumors, and the accumulation was inhibited by 2-(phosphonomethyl)pentanedioic acid (2-PMPA). Use of [(123)I]3 provided positive images of LNCaP tumors in single photon emission tomography scans. These results warrant further evaluation of [(123)I]3 and its derivatives as radiolabeled probes for the diagnosis of prostate cancer.

Focal positive prostate-specific membrane antigen (PSMA) expression in ganglionic tissues associated with prostate neurovascular bundle: Implications for novel intraoperative PSMA-based fluorescent imaging techniques

ObjectiveProstate specific membrane antigen (PSMA) is primarily expressed in glandular prostatic tissue and is frequently utilized to detect primary or metastatic prostatic adenocarcinoma (CaP). A purported novel application of PSMA detection is the intraoperative real-time identification of CaP using radioimmunoscintigraphy to define the extension of the surgical resection. Considering that PSMA expression has been reported in other tissues, we evaluated its immunoexpression in prostatic neurovascular bundle elements to assess the convenience and safety of the aforementioned procedure. Materials and methodsTwenty consecutive specimens of radical prostatectomy (RP) were retrieved from our surgical pathology archives. PSMA immunoexpression (Clone 3E6, DAKO) was assessed in a representative section from each specimen containing neurovascular bundle elements. ResultsPSMA expression was documented in 20/20 of examined CaP slides. Most cases exhibited an apical/cytoplasmic or cytoplasmic with membranous accentuation pattern of staining. Focal weak to moderate cytoplasmic staining was detected in associated ganglionic tissue in 3/15 of the examined RP. In all cases, staining was cytoplasmic, less extensive, and weaker than the pattern observed in CaP. None of the peripheral nerve sheath cells or lymphovascular components of the examined neurovascular bundles were positive for PSMA. ConclusionsWe found focal positive PSMA expression in the ganglionic cells of the prostatic neurovascular bundle. Our results suggest that the radioimmunoscintigraphic detection of radiolabeled PSMA antibodies might not be entirely specific for prostatic cells; this observation must be taken into account should an intraoperative PSMA-based fluorescent imaging technique be used to define the extension of the surgical procedure.