Quantitative evaluation of PSMA PET imaging using a realistic anthropomorphic phantom and shell-less radioactive epoxy lesions

Background Positron emission tomography (PET) with prostate specific membrane antigen (PSMA) have shown superior performance in detecting metastatic prostate cancers. Relative to [18F]fluorodeoxyglucose ([18F]FDG) PET images, PSMA PET images tend to visualize significantly higher-contrast focal lesions. We aim to evaluate segmentation and reconstruction algorithms in this emerging context. Specifically, Bayesian or maximum a posteriori (MAP) image reconstruction, compared to standard ordered subsets expectation maximization (OSEM) reconstruction, has received significant interest for its potential to reach convergence with minimal noise amplifications. However, few phantom studies have evaluated the quantitative accuracy of such reconstructions for high contrast, small lesions (sub-10 mm) that are typically observed in PSMA images. In this study, we cast 3 mm–16-mm spheres using epoxy resin infused with a long half-life positron emitter (sodium-22; 22Na) to simulate prostate cancer metastasis. The anthropomorphic Probe-IQ phantom, which features a liver, bladder, lungs, and ureters, was used to model relevant anatomy. Dynamic PET acquisitions were acquired and images were reconstructed with OSEM (varying subsets and iterations) and BSREM (varying β parameters), and the effects on lesion quantitation were evaluated. Results The 22Na lesions were scanned against an aqueous solution containing fluorine-18 (18F) as the background. Regions-of-interest were drawn with MIM Software using 40% fixed threshold (40% FT) and a gradient segmentation algorithm (MIM’s PET Edge+). Recovery coefficients (RCs) (max, mean, peak, and newly defined “apex”), metabolic tumour volume (MTV), and total tumour uptake (TTU) were calculated for each sphere. SUVpeak and SUVapex had the most consistent RCs for different lesion-to-background ratios and reconstruction parameters. The gradient-based segmentation algorithm was more accurate than 40% FT for determining MTV and TTU, particularly for lesions $$\le$$ ≤ 6 mm in diameter (R2 = 0.979–0.996 vs. R2 = 0.115–0.527, respectively). Conclusion An anthropomorphic phantom was used to evaluate quantitation for PSMA PET imaging of metastatic prostate cancer lesions. BSREM with β = 200–400 and OSEM with 2–5 iterations resulted in the most accurate and robust measurements of SUVmean, MTV, and TTU for imaging conditions in 18F-PSMA PET/CT images. SUVapex, a hybrid metric of SUVmax and SUVpeak, was proposed for robust, accurate, and segmentation-free quantitation of lesions for PSMA PET.

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

Objectives: To assess the frequency and intensity of [18F]-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 PET/CT or PET/MR imaging. Methods: One hundred twenty six patients undergoing [18F]-PSMA PET/CT or PET/MR imaging were retrospectively included. [18F]-PSMA activity (SUVmax) 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 SUVmax 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. Conclusions: 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.

Considerations on Integrating Prostate-Specific Membrane Antigen Positron Emission Tomography Imaging Into Clinical Prostate Cancer Trials by National Clinical Trials Network Cooperative Groups

PURPOSE As prostate-specific membrane antigen (PSMA) positron emission tomography (PET) becomes increasingly available in the United States, the greater sensitivity of the technology in comparison to conventional imaging poses challenges for clinical trials. The NCI Clinical Imaging Steering Committee (CISC) PSMA PET Working Group was convened to coordinate the identification of these challenges in various clinical scenarios and to develop consensus recommendations on how best to integrate PSMA PET into ongoing and upcoming National Clinical Trials Network (NCTN) trials. METHODS NCI CISC and NCI Genitourinary Steering Committee members and leadership nominated clinicians, biostatisticians, patient advocates, and other imaging experts for inclusion in the PSMA PET Working Group. From April to July 2021, the working group met independently and in conjunction with the CISC to frame challenges, including stage migration, response assessment, trial logistics, and statistical challenges, and to discuss proposed solutions. An anonymous, open-ended survey was distributed to members to collect feedback on challenges faced. Representatives from each NCTN group were invited to present an overview of affected trials. From these discussions, the consensus document was developed and circulated for the inclusion of multiple rounds of feedback from both the Working Group and CISC. RESULTS The current consensus document outlines the key challenges for clinical prostate cancer trials resulting from the increasing availability of PSMA PET. We discuss implications for patient selection and definition of end points and provide guidance and potential solutions for different clinical scenarios, particularly with regard to best practices in defining eligibility criteria and outcome measures. RECOMMENDATIONS This article provides guidance regarding clinical trial design and conduct, and the interpretation of trial results.

68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in Recurrent Prostate Cancer: Diagnostic Performance and Association with Clinical and Histopathological Data

The aim of the present study is to investigate and compare the performances of 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in identifying recurrent prostate cancer (PCa) after primary treatment and to explore the association of dual-tracer PET findings with clinical and histopathological characteristics. Thirty-five patients with biochemical relapse (BCR) of PCa underwent 68Ga PSMA PET/MRI for restaging purpose, with 31/35 also undergoing 68Ga-DOTA-RM2 PET/MRI scan within 16 days (mean: 3 days, range: 2–16 days). Qualitative and quantitative image analysis has been performed by comparing 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI findings both on a patient and lesion basis. Clinical and instrumental follow-up was used to validate PET findings. Fisher’s exact test and Mann-Whitney U test were used to investigate the association between dual-tracer PET findings, clinical and histopathological data. p-value significance was defined below the 0.05 level. Patients’ mean age was 70 years (range: 49–84) and mean PSA at time of PET/MR scans was 1.88 ng/mL (range: 0.21–14.4). A higher detection rate was observed for 68Ga-PSMA PET/MRI, with more lesions being detected compared to 68Ga-DOTA-RM2 PET/MRI (26/35 patients, 95 lesions vs. 15/31 patients, 41 lesions; p = 0.016 and 0.002). 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI findings were discordant in 11/31 patients; among these, 10 were 68Ga-PSMA positive (9/10 confirmed as true positive and 1/10 as false positive by follow-up examination). Patients with higher levels of PSA and shorter PSA doubling time (DT) presented more lesions on 68Ga-PSMA PET/MRI (p = 0.006 and 0.044), while no association was found between PET findings and Gleason score. 68Ga-PSMA has a higher detection rate than 68Ga-DOTA-RM2 in detecting PCa recurrence. The number of 68Ga-PSMA PET positive lesions is associated with higher levels of PSA and shorter PSA DT, thus representing potential prognostic factors.

Testicular metastasis in prostate cancer: A rare case of testicular metastasis diagnosed with 68Ga-PSMA and review of the literature

Objective: Testicular metastasis in prostate cancer is a rare entity. We aimed to report the case where this rare condition was diagnosed with Gallium prostate-specific membrane antigen–positron emission tomography/computed tomography (68Ga-PSMA-PET/CT). Subjects/patients and methods: A 68-year-old male with a prostate adenocarcinoma presented with testicular metastasis. The patient was diagnosed with 68Ga-PSMA-PET/CT, and bilateral inguinal orchiectomy was performed. Herein, our case is presented, and a short review of the literature is carried out. Conclusion: 68Ga-PSMA-PET/CT is an effective imaging method for detecting rare metastases. Level of evidence: 4

Changing Threshold-Based Segmentation Has No Relevant Impact on Semi-Quantification in the Context of Structured Reporting for PSMA-PET/CT

Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients imaged with 18F-PSMA-1007 PET/CT for primary staging and determined the stability of semi-quantitative parameters. Six hundred twenty-three lesions were categorized according to PSMA-RADS and manually segmented. In this context, PSMA-RADS-3A (soft-tissue) or -3B (bone) lesions are defined as being indeterminate for the presence of PC. For PMSA-RADS-4 and -5 lesions; however, PC is highly likely or almost certainly present [with further distinction based on absence (PSMA-RADS-4) or presence (PSMA-RADS-5) of correlative findings on CT]. Standardized uptake values (SUVmax, SUVpeak, SUVmean) were recorded, and volumetric parameters [PSMA-derived tumor volume (PSMA-TV); total lesion PSMA (TL-PSMA)] were determined using different maximum intensity thresholds (MIT) (40 vs. 45 vs. 50%). SUVmax was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories (p ≤ 0.0322). In particular, the clinically challenging PSMA-RADS-3A lesions showed significantly lower SUVmax and SUVpeak compared to the entire PSMA-RADS-4 or -5 cohort (p < 0.0001), while for PSMA-RADS-3B this only applies when compared to the entire PSMA-RADS-5 cohort (p < 0.0001), but not to the PSMA-RADS-4 cohort (SUVmax, p = 0.07; SUVpeak, p = 0.08). SUVmean (p = 0.30) and TL-PSMA (p = 0.16) in PSMA-RADS-5 lesions were not influenced by changing the MIT, while PSMA-TV showed significant differences when comparing 40 vs. 50% MIT (p = 0.0066), which was driven by lymph nodes (p = 0.0239), but not bone lesions (p = 0.15). SUVmax was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories in 18F-PSMA-1007 PET/CT. As such, the latter parameter may assist the interpreting molecular imaging specialist in assigning the correct PSMA-RADS score to sites of disease, thereby increasing diagnostic certainty. In addition, changes of the MIT in PSMA-RADS-5 lesions had no significant impact on SUVmean and TL-PSMA in contrast to PSMA-TV.