Concomitant Bilateral Inferior Gluteal Lymph Node Involvement in Metastatic Prostate Adenocarcinoma Detected on 68 Gallium-Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography.

An unusual and unique case of prostate adenocarcinoma with involvement of bilateral inferior gluteal lymph nodes is reported. The patient was a 42-year-old male, with conventional prostatic adenocarcinoma (Gleason score: 5 + 4 = 9), who, during disease progression with rising serum prostate specific antigen levels following medical androgen deprivation therapy, demonstrated new prostate-specific membrane antigen expressing metastatic intermuscular deposits in the bilateral gluteal region, subsequently proven to be bilateral inferior gluteal nodal metastasis. A therapeutic implication to this may be that these nodes usually fall beyond the range covered by the therapeutic radiation field coverage where external radiotherapy is the advocated modality of choice and are not easily reachable through standard surgical procedures. As a result, they could have an impact on the way patients are clinically treated and on their prognosis.

Unusual Metastatic Sites of Testis and Rectum in Prostate Cancer Detected by 68 Ga-PSMA-11 PET/CT Imaging at Initial Staging.

Imaging plays a pivotal role in defining the extent of disease and deciding therapeutic strategies in recently diagnosed high-risk prostate cancer. Standard-of-care conventional imaging may often miss rare metastatic disease sites. We herein present a unique case of prostate cancer where 68 Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT) detected two unusual metastatic sites (testis and rectum) in a single patient at initial staging, resulting in an accurate determination of the extent of disease, more tailored multimodal treatment planning, and exploration of the theragnostic potential.

68Ga-prostate specific membrane antigen-11 PET/CT versus multiparametric MRI in the detection of primary prostate cancer: A systematic review and head-to-head comparative meta-analysis.

PURPOSE: The goal of this study was to evaluate the effectiveness of two diagnostic methods, 68Ga-PSMA-11 PET/CT and mpMRI, in detecting primary prostate cancer without limitations on the Gleason score. METHODS: We conducted a comprehensive literature review, searching databases such as PubMed, Embase, and Web of Science until June 2023. Our objective was to identify studies that compared the efficacy of 68Ga-PSMA-11 PET/CT and mpMRI in detecting primary prostate cancer. To determine heterogeneity, the I2 statistic was used. Meta-regression analysis and leave-one-out sensitivity analysis were conducted to identify potential sources of heterogeneity. RESULTS: Initially, 1286 publications were found, but after careful evaluation, only 16 studies involving 1227 patients were analyzed thoroughly. The results showed that the 68Ga-PSMA-11 PET/CT method had a pooled sensitivity and specificity of 0.87 (95 % CI: 0.80-0.92) and 0.80 (95 % CI: 0.69-0.89), respectively, for diagnosing prostatic cancer. Similarly, the values for mpMRI were determined as 0.84 (95 % CI: 0.75-0.92) and 0.74 (95 % CI: 0.61-0.86), respectively. There were no significant differences in diagnostic effectiveness observed when comparing two primary prostate cancer methodologies (pooled sensitivity P = 0.62, pooled specificity P = 0.50). Despite this, the funnel plots showed symmetry and the Egger test results (P values > 0.05) suggested there was no publication bias. CONCLUSIONS: After an extensive meta-analysis, it was found that both 68Ga-PSMA-11 PET/CT and mpMRI demonstrate similar diagnostic effectiveness in detecting primary prostate cancer. Future larger prospective studies are warranted to investigate this issue further.

Prediction of T staging in PI-RADS 4-5 prostate cancer by combination of multiparametric MRI and 68Ga-PSMA-11 PET/CT.

BACKGROUND: In this study, we explored the diagnostic performances of multiparametric magnetic resonance imaging (mpMRI), 68 Ga-PSMA-11 PET/CT and combination of 68 Ga-PSMA-11 PET/CT and mpMRI (mpMRI + PET/CT) for extracapsular extension (ECE). Based on the analyses above, we tested the feasibility of using mpMRI + PET/CT results to predict T staging in prostate cancer patients. METHODS: By enrolling 75 patients of prostate cancer with mpMRI and 68 Ga-PSMA-11 PET/CT before radical prostatectomy, we analyzed the detection performances of ECE in mpMRI, 68 Ga-PSMA-11 PET/CT and mpMRI + PET/CT on their lesion images matched with their pathological sample images layer by layer through receiver operating characteristics (ROC) analysis. By inputting the lesion data into Prostate Imaging Reporting and Data System (PI-RADS), we divided the lesions into different PI-RADS scores. The improvement of detecting ECE was analyzed by net reclassification improvement (NRI). The predictors for T staging were evaluated by using univariate and multivariable analysis. The Kappa test was used to evaluate the prediction ability. RESULTS: One hundred three regions of lesion were identified from 75 patients. 50 of 103 regions were positive for ECE. The ECE diagnosis AUC of mpMRI + PET/CT is higher than that of mpMRI alone (ΔAUC = 0.101; 95% CI, 0.0148 to 0.1860; p < 0.05, respectively). Compared to mpMRI, mpMRI + PET/CT has a significant improvement in detecting ECE in PI-RADS 4-5 (NRI 36.1%, p < 0.01). The diagnosis power of mpMRI + PET/CT was an independent predictor for T staging (p < 0.001) in logistic regression analysis. In patients with PI-RADS 4-5 lesions, 40 of 46 (87.0%) patients have correct T staging prediction from mpMRI + PET/CT (κ 0.70, p < 0.01). CONCLUSION: The prediction of T staging in PI-RADS 4-5 prostate cancer patients by mpMRI + PET/CT had a quite good performance.

Detection Efficacy of 68Ga-PSMA-11 PET/CT in Biochemical Recurrence of Prostate Cancer with Very Low PSA Levels: A 7-Year, Two-Center "Real-World" Experience.

In biochemical recurrence of prostate cancer (BCR), prompt tumor localization guides early treatment, potentially improving patient outcomes. Gallium-68 prostate-specific membrane antigen-11 positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) detection rates of lesions suspicious for prostate cancer are well known to rise along with prostate-specific antigen (PSA) concentration. However, published data are limited regarding very low values (≤0.2 ng/mL). We retrospectively analyzed ~7-year "real-world" experience in this setting in a large post-prostatectomy cohort (N = 115) from two academic clinics. Altogether 44 lesions were detected in 29/115 men (25.2%) (median [minimum-maximum] 1 [1-4]/positive scan). The apparent oligometastatic disease was found in nine patients (7.8%) at PSA as low as 0.03 ng/mL. Scan positivity rates were highest when PSA was >0.15 ng/mL, PSA doubling time was ≤12 months, or the Gleason score was ≥7b (in 83 and 107 patients, respectively, with available data); these findings were statistically significant (p ≤ 0.04), except regarding PSA level (p = 0.07). Given the benefits of promptly localizing recurrence, our observations suggest the potential value of 68Ga-PSMA-11 PET/CT in the very low PSA BCR setting, especially in cases with more rapid PSA doubling time or with high-risk histology.

Special issue "The advance of solid tumor research in China": 68Ga-PSMA-11 PET/CT for evaluating primary and metastatic lesions in different histological subtypes of renal cell carcinoma.

Conventional imaging examinations are not sensitive enough for the early detection of recurrent or metastatic lesions in renal cell carcinoma (RCC) patients. We aimed to explore the role of 68 Ga-prostate specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (CT) in the detection of primary and metastatic lesions in such patients. We retrospectively analyzed 50 RCC patients who underwent 68 Ga-PSMA-11 PET/CT from November 2017 to December 2020. We observed a higher median accuracy and tumor-to-background maximum standard uptake value (SUVmax ) ratio (TBR) of 68 Ga-PSMA-11 PET/CT in clear cell RCC (ccRCC; 96.57% and 6.00, respectively) than in non-clear cell RCC (ncRCC; 82.05% and 2.99, respectively). The accuracies in detecting lesions in the renal region, bone, lymph nodes and lungs in ccRCC were 100.00%, 95.00%, 98.08% and 75.00%, respectively, and those in the renal region, bone and lymph nodes in ncRCC were 100.00%, 86.67% and 36.36%, respectively. The median TBRs of the lesions from the above locations were 0.38, 10.96, 6.69 and 13.71, respectively, in ccRCC and 0.13, 4.02 and 0.73, respectively, in ncRCC. The PSMA score evaluated with immunohistochemistry was correlated with the SUVmax (P = .046) in RCC. Higher PSMA scores were observed in ccRCC than in ncRCC (P = .031). 68 Ga-PSMA-11 PET/CT resulted in changes in clinical management in 12.9% (4/31) of cases because of the discovery of new metastases not detected with conventional imaging. These results indicate that 68 Ga-PSMA-11 PET/CT is a promising method for the detection of metastatic lesions in ccRCC, especially for those in the bone and lymph nodes.

Prognostic Role of 68Ga-PSMA11 PET-Based Response in Patients with Prostate Cancer Undergoing Taxane-Based Chemotherapy.

This study was performed to assess the prognostic utility of conventional biochemical and imaging response criteria and 68Ga-PSMA11 PET-adapted or -specific systems regarding overall survival (OS) in men with metastatic hormone-sensitive and castration-resistant prostate cancer (PC) treated with taxane-based chemotherapy. Methods: A total of 103 patients (metastatic hormone-sensitive PC, n = 57; castration-resistant PC, n = 46) underwent taxane-based chemotherapy. All patients had a minimum of 2 prostate-specific membrane antigen (PSMA) PET scans (at baseline and up to 3 mo after treatment). PSMA PET response was assessed by RECIST 1.1, adapted Prostate Cancer Working Group Criteria 3 (using PSMA PET instead of bone scan), aPERCIST, and PSMA PET progression (PPP) criteria. Response by each criterion was stratified by either progressive disease (PD) or non-PD. For aPERCIST, stratification by PD, stable disease (SD), and partial/complete remission (PR/CR) was performed. Biochemical response was determined by a prostate-specific antigen decrease of at least 50%. Subgroup analyses were performed by castration status. Univariable Cox proportional hazards regression analyses including Harrell's concordance indices were calculated to investigate the association of PD by response criteria and OS. Kaplan-Meier tests including log-rank statistics were calculated for survival analyses. Results: Twenty-six (25%) patients had unmeasurable disease by RECIST 1.1. PD by any response criterion was associated with an at least 2.5-fold increased risk of death and was highest for PD versus CR/PR by aPERCIST (hazard ratio, 11.4) on univariable regression. Stratified by castration status, a similar pattern was observed. PD by any criterion as associated with significantly shortened OS across overall and subgroup analyses. PR/CR by aPERCIST identified patients with lower risk of death and longer OS compared with patients with PD or SD. Conclusion: PSMA PET-based response criteria (PPP, aPERCIST, adapted Prostate Cancer Working Group Criteria 3) have high prognostic utility in men with metastatic PC undergoing taxane-based chemotherapy. PPP is simple to use, identified most patients with PD, and showed best prognostic utility regarding OS. PR/CR by aPERCIST identifies a subgroup of responders (PR/CR) showing better outcomes than patients with PD or SD. Future studies are warranted to amend the current paradigm relying on mere differentiation of PD versus non-PD in metastatic PC and to identify true treatment responders by imaging criteria.

18F-FDG PET/CT Versus 68Ga-PSMA-11 PET/CT in Evaluation of Distant Metastatic Disease in Recurrent Renal Cell Carcinoma.

Prostate-specific membrane antigen (PSMA) expression has been observed in the neovasculature of various malignancies. We present a case of metastatic renal cell carcinoma (RCC) with comparative 18F-FDG PET/CT and 68Ga-PSMA-11 imaging in which FDG PET/CT failed to detect metastatic thyroid disease and showed less 18F-FDG-concentrating lesions at other sites, whereas 68Ga-PSMA-11 PET/CT identified metastatic thyroid disease and demonstrated intensely 68Ga-PSMA-11-expressing distant metastatic lesions. 68Ga-PSMA-11 PET/CT may be considered a potentially useful imaging technique in RCC to detect metastasis and to guide the choice of specific treatments, such as PSMA-based radionuclide therapy in patients with recurrent metastatic RCC.

Low TLR and PSMA-TV predict biochemical response to abiraterone acetate in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage.

OBJECTIVE: To explore whether 68Ga-PSMA-11 PET/CT-derived parameters could predict biochemical response to abiraterone acetate (AA) treatment and prognosis in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage. METHODS: The clinicopathologic data of 106 mCRPC cases receiving AA treatment were retrospectively analyzed. Logistic regression analysis was used to determine the independent predictors of biochemical response to AA treatment. Cox analyses were applied to investigate the independent prognostic factors for time to biochemical progression (TTBP) and radiological progression-free survival (rPFS). Survival analysis and ROC curve were also used. RESULTS: Multivariable Logistic analysis demonstrated that prior ADT duration ≥ 12 months, low prostate specific membrane antigen receptor-expressing tumor volume (PSMA-TV), low tumor to liver ratio (TLR) were independent predictors of biochemical response to AA treatment. Multivariate Cox analysis demonstrated that low PSMA-TV and low TLR were independent prognostic factors of longer TTBP and rPFS. The TTBP and rPFS of patients with higher PSMA-TV or TLR were significantly decreased compared with that of patients with lower PSMA-TV and TLR. The area under ROC curve (AUC) of combining ADT duration, PSMA-TV and TLR was 0.82 for predicting biochemical response to AA, which was significantly increased compared with that of other 68Ga-PSMA-11 PET/CT-derived parameters alone. CONCLUSIONS: Low PSMA-TV, low TLR were vital independent predictors of biochemical response to AA treatment and were associated with preferable prognosis in mCRPC patients. Combining ADT duration, PSMA-TV and TLR performed well in distinguishing AA responders from non-responders in mCRPC patients.

The value of gallium-68 prostate-specific membrane antigen PET/CT and 2-[18F]fluoro-2-deoxy-D-glucose PET/CT in the detection of thyroid cancer lesions: a prospective head-to-head comparison.

OBJECTIVE: Thyroid cancer is increasing in incidence. Prostate-specific membrane antigen (PSMA) targeted radionuclide imaging and treatment demonstrated remarkable value in prostate cancer patients. Studies have shown that PSMA is also expressed in thyroid cancer. Our purpose is to evaluate the clinical usefulness of [68Ga]Ga-PSMA-11 PET/CT for the diagnosis of thyroid cancer. METHODS: We enrolled 23 DTC and 17 RAIR-DTC patients prospectively. All patients underwent [68Ga]Ga-PSMA-11 PET/CT and 2-[18F]FDG PET/CT. PSMA expression was determined by immunohistochemistry on histological samples of lymphatic metastasis of 12 patients. We compared the detection rates and semi-quantitative parameters between [68Ga]Ga-PSMA-11PET/CT and 2-[18F]FDG PET/CT. RESULTS: A total of 72 lesions were detected. Detection rates of DTC and RAIR-DTC by [68Ga]Ga-PSMA-11 PET/CT were lower than those by 2-[18F]FDG PET/CT (60.00% vs. 90.00%, P = .004; 59.38% vs. 96.88%). Compared with DTC, RAIR-DTC had higher semi-quantitative parameters of 2-[18F]FDG PET/CT. There was no significant difference in semi-quantitative parameters of [68Ga]Ga-PSMA-11 PET/CT between DTC and RAIR-DTC. Immunohistochemistry showed a significantly higher PSMA expression for RAIR-DTC than for DTC. However, there was no significant correlation between PSMA expression and SUVmax on 68Ga-PSMA [68Ga]Ga-PSMA-11 PET/CT. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT can detect thyroid cancer metastases but its detection rate was lower than that of 2-[18F]FDG PET/CT. There was a difference in PSMA expression levels between DTC and RAIR-DTC, but the difference was not reflected on [68Ga]Ga-PSMA-11 PET/CT. ADVANCES IN KNOWLEDGE: [68Ga]Ga-PSMA-11 PET/CT has potential value in the diagnosis of thyroid cancer. [68Ga]Ga-PSMA-11 PET/CT could screen out patients who may benefit from PSMA-targeted radionuclide therapy.

Super Early Scan of PSMA PET/CT in Evaluating Primary and Metastatic Lesions of Prostate Cancer.

68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT has been widely used in the diagnosis of prostate cancer (PCa); however, the urine lead shielding resulting from the urinary metabolism of tracers may obstruct the detection of surrounding metastasis. In this research, the additive value of super early scanning in diagnosing primary lesions and metastasis in the pelvic cavity was evaluated. Firstly, the differentiation efficiency of 68Ga-PSMA-11 PET scanned at 3 min post-injection (min P.I.) was measured in PSMA-positive (22rv1 cells) and PSMA-negative (PC3 cells) model mice. Secondly, 106 patients were scanned at 3 min P.I. for the pelvic cavity and then scanned as a standard protocol at 45 min P.I. In the results, the differential diagnosis of PSMA expression was completely reflected as early as 3 min P.I. for mice models. For patients, when correlated with the Gleason score, the quantitative results of the super early scan displayed a comparable correlation coefficient with the routine scan. The target to bladder ratios increased from 1.44 ± 2.40 at 45 min to 10.10 ± 19.10 at 3 min (p < 0.001) for the primary lesions, and it increased from 0.99 ± 1.88 to 9.27 ± 23.03 for metastasis. Meanwhile, the target to background ratios increased from 2.21 ± 2.44 at 3 min to 19.13 ± 23.93 at 45 min (p < 0.001) for the primary lesions, and it increased from 1.68 ± 2.71 to 12.04 ± 18.73 (p < 0.001) for metastasis. In conclusion, super early scanning of 68Ga-PSMA-11 PET/CT added referable information for metastasis detection in order to avoid disturbing tracer activity in the urinary system.

68Ga-PSMA-11 PET/CT Parameter Correlates with Pathological VEGFR-2/PDGFR-ß Expression in Renal Cell Carcinoma Patients.

BACKGROUND: Response prediction is necessary for renal cell carcinoma (RCC) tumors. We aim to evaluate parameters derived from 68 Ga-PSMA-11 PET/CT images for prediction of pathological VEGFR-2/PDGFR-ß expression of primary RCC tumors. METHODS: Forty-eight RCC patients were retrospectively enrolled with preoperative 68 Ga-PSMA-11 PET/CT scan and surgical specimen. Radiological parameters including tumor diameter, mean CT value, and maximal standard uptake value (SUVmax) were derived from PET/CT images and pathological VEGFR-2/PDGFR-ß/PSMA expression were identified with immunohistochemistry. Mann-Whitney U test was performed for continuous variables and the chi-square test for categorical variables. ROC was used for determining the effectiveness of preoperative parameters in differentiating VEGFR-2/PDGFR-ß expression. Univariate and multivariate logistic regression analyses were performed for significant parameters to predict VEGFR-2 & PDGFR-ß co-expression. RESULTS: Of the 48 tumors, 25 (52.1%) harbored positive VEGFR-2 expression, 28 (58.3%) harbored positive PDGFR-ß expression, and 24 (50%) were both VEGFR-2 positive and PDGFR-ß positive. SUVmax significantly differed by subgroups of VEGFR-2/PDGFR-ß expression (both P < 0.001). SUVmax demonstrated superior performance for differentiating VEGFR-2 & PDGFR-ß co-expression (positive vs. negative), with area under the curve 0.87 (95% CI 0.78-0.96, P < 0.001), sensitivity 93% and specificity 78%. Moreover, SUVmax was identified as the significant predictor for VEGFR-2 & PDGFR-ß co-expression (odds ratio 4.01, 95% CI 1.99-8.08, P < 0.001). Concordant with radiological findings with 68 Ga-PSMA-11 PET/CT, pathological PSMA staining intensity was significantly higher in both VEGFR-2-positive tumor and PDGFR-ß-positive tumor (P = 0.009 and P < 0.001, respectively). CONCLUSION: 68 Ga-PSMA-11 PET/CT could effectively identify pathological VEGFR-2/PDGFR-ß expression of primary RCC tumors, which may help with selection of mRCC patients suitable for TKIs treatment.

Head-To-Head Comparison of 68Ga-PSMA-11 PET/CT and 99mTc-MDP Bone Scintigraphy for the Detection of Bone Metastases in Patients With Prostate Cancer: A Meta-Analysis.

BACKGROUND. Bone scintigraphy (BS) using 99mTc-labeled methylene diphospho-nate (99mTc-MDP) remains the recommended imaging modality for the detection of bone metastases in patients with prostate cancer (PCa). However, PET/CT using prostate-specific membrane antigen (PSMA) ligands is increasingly recognized as a means of evaluating disease extent in patients with PCa, including use as a possible stand-alone test in high-risk patients. OBJECTIVE. The purpose of this study is to compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with that of 99mTc-MDP BS for the detection of bone metastases in patients with PCa. EVIDENCE ACQUISITION. The PubMed, Embase, and Cochrane Library databases were searched through October 2021 to identify studies reporting a head-to-head comparison of 68Ga-PSMA-11 PET/CT and 99mTc-MDP BS for the detection of bone metastases in patients with PCa. Only studies with a well-defined reference standard (including various combinations of imaging and/or clinical follow-up) were included. Pooled diagnostic performance was calculated using a bivariate random-effects model, and an AUC was derived for each test from hierarchic summary ROC analysis. The complementary roles of the two tests in identifying bone metastases in patients in whom one of the tests was negative were summarized. EVIDENCE SYNTHESIS. Six studies with 546 patients were included. Pooled sensitivity and specificity, respectively, were 98% (95% CI, 94-99%) and 97% (95% CI, 91-99%) for 68Ga-PSMA-11 PET/CT versus 83% (95% CI, 69-91%) and 68% (95% CI, 41-87%) for 99mTc-MDP BS. The AUC was 0.99 (95% CI, 0.96-1.00) for 68Ga-PSMA-11 PET/CT and 0.85 (95% CI, 0.81-0.87) for 99mTc-MDP BS. Among 408 patients from five included studies, 68Ga-PSMA-11 PET/CT correctly identified bone metastases in 43 of 193 patients (22.3%) with negative 99mTc-MDP BS results, whereas 99mTc-MDP BS correctly identified bone metastases in four of 210 patients (1.9%) with negative 68Ga-PSMA-11 PET/CT results. CONCLUSION. On a per-patient basis, the diagnostic performance of 68Ga-PSMA-11 PET/CT is superior to that of 99mTc-MDP BS for the detection of PCa bone metastases. Furthermore, 99mTc-MDP BS offers limited additional information in patients with negative 68Ga-PSMA-11 PET/CT results. CLINICAL IMPACT. According to current evidence, 99mTc-MDP BS is highly unlikely to be additive to 68Ga-PSMA-11 PET/CT in identifying bone metastases in patients with PCa.

Differential tumor biology between locoregional and distant metastasis in a patient with TENIS with TKI-resistant aggressive recurrent disease: a comparative evaluation with FDG, 68Ga-DOTATATE and 68Ga-PSMA-11 PET-CT.

The molecular PET-CT imaging profile of an interesting case of differentiated thyroid carcinoma, later transformed into with thyroglobulin elevation and negative iodine scintigraphy (TENIS) with tyrosine kinase inhibitor (TKI) resistant recurrent aggressive disease, is presented. The patient was evaluated to assess SSTR-2 or PSMA expression to explore the possibility of any effective targeted nuclear therapy. 18F-FDG, 68Ga-DOTATATE and 68Ga-PSMA-11 PET/CT was performed, which revealed tracer avidity in all 3 scans in the extensive loco-regional disease of large ill-defined retropharyngeal and retro-tracheal soft tissue eroding cricoid cartilage, extending into tracheal lumen and left sided strap muscles. On the contrary, there was no definite uptake in the multiple bilateral lung nodules, the scan findings indicating a differential tumor biology between loco-regional and distant metastasis.

Head-to-Head Comparison of 68Ga-PSMA-11 PET/CT and Multiparametric MRI for Pelvic Lymph Node Staging Prior to Radical Prostatectomy in Patients With Intermediate to High-Risk Prostate Cancer: A Meta-Analysis.

PURPOSE: To compare the diagnostic performance of 68Ga-PSMA-11 PET/CT and mpMRI for pelvic lymph node staging prior to radical prostatectomy in prostate cancer (PCa) patients based on per patient data. METHODS: PubMed and Embase databases were searched until October 2020 for eligible studies evaluating head-to-head comparison of 68Ga-PSMA-PET/CT and mpMRI for the detection of pelvic lymph node metastases (PLNMs) using pelvic lymph node dissection (PLND) as gold standard. The pooled sensitivity, specificity, and area under the summary receiver-operating characteristics curve (AUC) were determined for the two imaging modalities. RESULTS: Nine studies with 640 patients were included. The pooled sensitivity, specificity, and AUC for 68Ga-PSMA-11 PET/CT vs. mpMRI were 0.71 (95% CI: 0.48-0.86) vs. 0.40 (95% CI: 0.16-0.71), 0.92 (95% CI: 0.88-0.95) vs. 0.92 (95% CI: 0.80-0.97), and 0.92 (95% CI: 0.88-0.95) vs. 0.82 (95% CI: 0.79-0.86), respectively. There was substantial heterogeneity for both imaging modalities, and meta-regression analysis revealed that the number of patients, prevalence of PLNMs, PSA level, reference standard, and risk classification might be the potential causes of heterogeneity. CONCLUSION: This meta-analysis of head-to-head comparison studies confirms that there is a trend toward a higher sensitivity and diagnostic accuracy of 68Ga-PSMA-11 PET/CT compared to mpMRI for the detection of PLNMs in PCa patients. Nevertheless, according to current guidelines, PLND still needs to be recommended in case of negative results from 68Ga-PSMA-11 PET/CT due to significant risk of malignancy.

Response Assessment and Prediction of Progression-Free Survival by 68Ga-PSMA-11 PET/CT Based on Tumor-to-Liver Ratio (TLR) in Patients with mCRPC Undergoing 177Lu-PSMA-617 Radioligand Therapy.

At present, little is known about the molecular imaging-based response assessment of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with 177Lutetium (177Lu-PSMA-617 RLT) in metastatic castration-resistant prostate cancer (mCRPC). Our study evaluated the response to RLT using both molecular imaging and biochemical response assessments, and their potential prediction of progression-free survival (PFS). Fifty-one consecutive patients given two cycles of RLT at 6-week intervals were analyzed retrospectively. 68Ga-PSMA-11 PET/CT was obtained about 2 weeks prior to the first and 4-6 weeks after the second cycle. Molecular imaging-based response using SUVpeak and tumor-to-liver ratio (TLR) was determined by modified PERCIST criteria. ∆TLR and ∆SUV were significantly correlated with ∆PSA (p < 0.001, each). After a median follow-up of 49 months, the median PFS (95% CI) was 8.0 (5.9-10.1) months. In univariate analysis, responders showing partial remission (PRPSA and PRTLR) had significantly (p < 0.001, each) longer PFS (median: 10.5 and 9.3 months) than non-responders showing either stable or progressive disease (median: 4.0 and 3.5 months). Response assessment using SUVpeak failed to predict survival. In multivariable analysis, response assessment using TLR was independently associated with PFS (p < 0.001), as was good performance status (p = 0.002). Molecular imaging-based response assessment with 68Ga-PSMA-11 PET/CT using normalization of the total lesion PSMA over healthy liver tissue uptake (TLR) could be an appropriate biomarker to monitor RLT in mCRPC patients and to predict progression-free survival (PFS) of this treatment modality.

Correlation of Lesional Uptake Parameters and Ratios with miPSMA Score and Estimating Normal Physiologic Concentration: An Exploratory Analysis in Metastatic Castration-Resistant Prostatic Carcinoma Patients with 68Ga-PSMA-11 PET/CT.

The use of prostate-specific membrane antigen (PSMA)-based PET/CT has grown rapidly in recent years. This study estimated lesional uptake, normal physiologic concentrations, and temporal variation on delayed PET/CT of 68Ga-PSMA-11 across different molecular imaging PSMA (miPSMA) expression scores in patients with metastatic castration-resistant prostatic carcinoma. Methods: We retrospectively studied 50 patients who were evaluated for 177Lu-PSMA-targeted radioligand therapy and underwent 68Ga-PSMA-11 PET/CT to determine disease status. Their mean age was 67.5 ± 8 y (52-84 y), and their average serum prostate-specific antigen level was 401 ± 1,353 ng/mL (0.098-9,235.13 ng/mL) at the time of scanning. They underwent standard 68Ga-PSMA-11 PET/CT an average of 65 min after injection (60-90 min). Tumors (n = 50) were correlated with miPSMA expression score and uptake. Physiologic tracer distribution was estimated by placing a volume of interest 1 cm in diameter for smaller organs (submandibular, parotid, lacrimal, and tubarial glands; renal cortices; blood pool; and bowel) and 3 cm for larger organs (liver and spleen). SUVmax and SUVmean were estimated for each region. Tumor-to-spleen (T/S), tumor-to-liver (T/L), and tumor-to-parotid (T/P) ratios were calculated for each lesion. For 16 patients who underwent a delayed scan an average of 135 min after injection (120-150 min), additional analysis evaluated the effect of the delay. Results: Uptake was maximal in renal cortices, followed by salivary glands, bowel, spleen, liver, lacrimal glands, and blood pool. SUVmax averaged 37.7 ± 22.1 for renal cortices, 15.4 ± 7.3 for submandibular glands, 14.4 ± 7.1 for parotid glands, 9.4 ± 4.9 for spleen, 6.2 ± 3.7 for lacrimal glands, 5.9 ± 2.3 for liver, 5.3 ± 1.41 for tubarial glands, 13.8 ± 7.6 for bowel, and 2.4 ± 1.9 for blood pool. SUVmax averaged 10.33 ± 3.27 (6.46-17) for miPSMA expression score 2 and 38.21 ± 25.9 (7.68-119.08) for score 3. T/S and T/P ratios averaged 1.21 ± 0.44 (0.48-2.04) and 0.6 ± 0.18 (0.39-0.87), respectively, for score 2 and 5.05 ± 4.46 (1.25-20.89) and 3.15 ± 2.09 (1.06-9.45), respectively, for score 3. SUVmax for score 3 lesions averaged 18.85, which increased significantly to 26.24 on delayed imaging (P = 0.0001). However, T/L, T/S, and T/P ratios did not significantly change. Temporal variation in normal organs showed SUVmax to increase significantly on delayed scans for salivary (submandibular and parotid) and lacrimal glands and renal cortices, whereas SUVmean increased significantly for spleen; liver; and parotid, tubarial, and lacrimal glands and insignificantly for other organs. Conclusion: These data form a basis for a proposed consensus on standard reference ranges for quantitative 68Ga-PSMA-11 PET/CT. The temporal variations should be kept in mind for delayed acquisitions; T/S, T/L, and T/P ratios might serve as better markers for such scenarios.

Intra-patient comparison of physiologic 68Ga-PSMA-11 and 18F-DCFPyL PET/CT uptake in ganglia in prostate cancer patients: a pictorial essay.

BACKGROUND: Recent studies reported metabolic uptake in at least one of the evaluated ganglia in 98.5% of patients undergoing 68Ga -PSMA-11 and in 96.9% of patients undergoing 18F-DCFPyL PET/CT examination. We have observed different patterns of ganglion visualization with 18F-DCFPyL compared to 68Ga-PSMA-11. This includes more frequent visualization of cervical and sacral ganglia, which may be attributable to better imaging characteristics with 18F PET imaging. CASE PRESENTATION: This pictorial essay is to illustrate and compare, in the same patient, various representative cases of 68Ga-PSMA-11 and 18F-DCFPyL PET/CT uptake in ganglia at different anatomic locations, with different patterns and distribution of metabolic activity. CONCLUSION: Reading physicians should be aware of the frequently encountered and occasionally different physiologic uptake of 68Ga-PSMA-11 and 18F DCFPyL in different ganglia.

Comprehensive evaluation of 68Ga-PSMA-11 PET/CT parameters for discriminating pathological characteristics in primary clear-cell renal cell carcinoma.

PURPOSE: To evaluate parameters derived from 68Ga-PSMA-11 PET/CT images for discriminating pathological characteristics in primary clear-cell renal cell carcinoma (ccRCC). METHODS: The study retrospectively examined data for 36 ccRCC patients with preoperative 68Ga-PSMA-11 PET/CT scan and surgical specimens. Radiological parameters including maximal tumor diameter, mean CT value, and maximal standard uptake value (SUVmax) were derived from PET/CT images. Pathological characteristics included WHO/ISUP grade and adverse pathology (tumor necrosis or sarcomatoid or rhabdoid feature). Values of radiological parameters were compared within subgroups of pathological characteristics. Receiver operating characteristic (ROC) curve analysis was used for the effectiveness of radiological parameters in differentiating pathological characteristics, estimating area under the ROC curve (AUC) and 95% confidence intervals (CIs). RESULTS: The WHO/ISUP grade distribution for 36 tumors was grade 1, 9 (25.0%); grade 2, 12 (33.3%); grade 3, 9 (25.0%); and grade 4, 6 (16.7%). Adverse pathology was positive for 15 (41.7%). Radiological tumor diameter and SUVmax significantly differed by WHO/ISUP grade, pT stage, and adverse pathology (all P < 0.05), with no difference by CT value. Tumor diameter demonstrated sensitivity 86% and specificity 88% for pT stage, with cutoff 6.70 and AUC 0.91 (95% CI, 0.79-1.00, P < 0.001). SUVmax could effectively differentiate WHO/ISUP grade (3-4 vs. 1-2) and adverse pathology (positive vs. negative), with AUC 0.89 (95% CI, 0.81-0.98, P < 0.001), cutoff 16.4, sensitivity 100%, and specificity 71% and AUC 0.92 (95% CI, 0.85-0.99, P < 0.001), cutoff 18.5, sensitivity 94%, and specificity 87%, respectively. CONCLUSION: 68Ga-PSMA-11 PET/CT could effectively identify aggressive pathological features of ccRCC.

Comparison of Dual-Tracer PET and CT Features to Conventional Risk Categories in Assessing Response to 177Lu-PSMA-617 Therapy for Metastatic Prostate Adenocarcinoma with Urinary Bladder Involvement.

The present communication details the imaging characteristics, peculiarities, and response to 177Lu-labeled prostate-specific membrane antigen (PSMA)-617-targeted radioligand therapy (PRLT) in accordance with Gleason score and use of dual-tracer PET (68Ga-PSMA-11 and 18F-FDG) in patients with urinary bladder invasion or metastasis by prostate cancer, including the prognostic value of 18F-FDG PET in predicting response to treatment. The CT attenuation units (Hounsfield units) correlated with the prostate primary in the case of direct tumor extension from the prostate, whereas in hematogenous metastatic seeding the Hounsfield units were lower than in the primary prostatic tumor. A favorable outcome to 177Lu-PSMA-617 PRLT was observed in patients with low or no baseline 18F-FDG uptake despite a high Gleason score and a high-risk National Comprehensive Cancer Network prognostic category and did not correlate with the latter alone, whereas a high SUVmax on 18F-FDG PET/CT was associated with an adverse outcome. These findings suggest a promising role for 18F-FDG PET/CT in predicting therapeutic outcomes more confidently, and hence the concept of dual-tracer PET appears to hold good in prostate adenocarcinoma theranostics.