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Background Intravenous prostate-specific membrane antigen (PSMA)-targeted radioligand therapy improves survival in men with metastatic castration-resistant prostate cancer. Yet, the impact of selective prostatic arterial administration on primary tumor uptake is unclear. Purpose To compare gallium 68 (68Ga)-PSMA-11 uptake using dynamic PET/CT in prostatic tumoral volumes of interest (VOIs) during intravenous and selective prostatic arterial infusions for individuals with untreated, high-risk prostate cancer. Materials and Methods In this prospective, intraindividual comparative study conducted at an academic medical center, five men aged 58, 61, 64, 66, and 68 years with treatment-naive prostate cancer were enrolled between January 2022 and February 2023 and underwent two dynamic 68Ga-PSMA-11 PET/CT examinations 1 week apart. During the first examination, the radiotracer was administered intravenously. During the second administration, the radiotracer was delivered into either the right or left prostatic artery through an angiographically placed microcatheter. The primary outcome was maximum standardized uptake value (SUVmax) in prostatic tumoral VOIs. The secondary outcomes included mean SUV (SUVmean) in prostatic tumoral VOIs and area under the SUVmean curves (AUC). Longitudinal mixed-effects models were used to compare dynamic SUVmax and SUVmean time-activity curves (TACs), and paired t tests were used for the remaining data. Results The mean SUVmax within tumoral VOIs was 14 (range, 3-43) for venous sessions and 938 (range, 460-1436) for arterial sessions (P = .008). The SUVmean within VOIs was greater during arterial sessions (P < .001) overall and 46-fold and 19-fold greater at peak uptake and final time points, respectively. The mean AUC was greater on arterial TACs than on venous TACs at 14600 SUV × min (range, 8353-20025 SUV × min) and 240 SUV × min (range, 69-622 SUV × min), respectively (P = .002). Conclusion Selective prostatic arterial infusion resulted in greater 68Ga-PSMA-11 tumoral SUV than intravenous infusion. Further study of local-regional, intra-arterial delivery of a PSMA-targeted theranostic agent is warranted in high-risk prostate cancer. ClinicalTrials.gov identifier: NCT04976257 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Civelek in this issue.

Since the development of fibroblast activation protein-targeted radiopharmaceuticals, 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT has been found to be suitable for detecting primary and metastatic lesions in many types of tumors. However, there is currently a lack of reliable data regarding the clinical impact of this family of probes. To address this gap, the present study aimed to analyze the clinical impact of 68Ga-FAPI PET/CT by examining a large cohort of patients with various tumors. Methods: In total, 226 patients (137 male and 89 female) were included in this retrospective analysis. Pancreatic cancer and head and neck cancers were the most common tumor types in this cohort. TNM stage and oncologic management were initially determined with gold standard imaging, and these results were compared with 68Ga-FAPI PET/CT. Changes were classified as major and minor. Results: For 42% of all patients, TNM stage was changed by 68Ga-FAPI PET/CT results. Most of these changes resulted in upstaging. A change in clinical management occurred in 117 of 226 patients. Although a major change in management occurred in only 12% of patients, there was a significant improvement in the ability to accurately plan radiation therapy. In general, the highest clinical impact of 68Ga-FAPI PET/CT imaging was found in patients with lung cancer, pancreatic cancer, and head and neck tumors. Conclusion: 68Ga-FAPI PET/CT is a promising imaging probe that has a significant impact on TNM stage and clinical management. 68Ga-FAPI PET/CT promises to be a crucial new technology that will improve on conventional radiologic imaging methods such as contrast-enhanced CT and contrast-enhanced MRI typically acquired for cancer staging.

PURPOSE: The proPSMA trial at ten Australian centers demonstrated increased sensitivity and specificity for PSMA PET/CT compared to conventional imaging regarding metastatic status in primary high-risk prostate cancer patients. A cost-effectiveness analysis showed benefits of PSMA PET/CT over conventional imaging for the Australian setting. However, comparable data for other countries are lacking. Therefore, we aimed to verify the cost-effectiveness of PSMA PET/CT in several European countries as well as the USA. METHODS: Clinical data on diagnostic accuracy were derived from the proPSMA trial. Costs for PSMA PET/CT and conventional imaging were taken from reimbursements of national health systems and individual billing information of selected centers in Belgium, Germany, Italy, the Netherlands, and the USA. For comparability, scan duration and the decision tree of the analysis were adopted from the Australian cost-effectiveness study. RESULTS: In contrast to the Australian setting, PSMA PET/CT was primarily associated with increased costs in the studied centers in Europe and the USA. Mainly, the scan duration had an impact on the cost-effectiveness. However, costs for an accurate diagnosis using PSMA PET/CT seemed reasonably low compared to the potential consequential costs of an inaccurate diagnosis. CONCLUSION: We assume that the use of PSMA PET/CT is appropriate from a health economic perspective, but this will need to be verified by a prospective evaluation of patients at initial diagnosis.

[ 68Ga]Ga-PSMA-11 ( 68Ga-PSMA-11) is used to identify prostate-specific membrane antigen (PSMA)-positive tumors on PET scans. In the VISION study, 68Ga-PSMA-11 was used to determine the eligibility of patients with metastatic castration-resistant prostate cancer for treatment with [177Lu]Lu-PSMA-617 (177Lu-PSMA-617), based on predefined read criteria. This substudy aimed to investigate the interreader variability and intrareader reproducibility of visual assessments of 68Ga-PSMA-11 PET/CT scans using the VISION read criteria and evaluate the agreement between read results for this and the VISION study. Methods: In VISION, 68Ga-PSMA-11 PET/CT scans were centrally read as inclusion cases if they had at least 1 PSMA-positive lesion and no PSMA-negative lesions that fulfilled the exclusion criteria. In this substudy, 125 PET/CT scans (75 inclusion and 50 exclusion cases) were randomly selected from VISION and retrospectively assessed by 3 independent central readers. A random subset of 20 cases (12 inclusion and 8 exclusion cases) was recoded for assessment of intrareader reproducibility. Classification of cases as inclusion or exclusion cases was based on the VISION read criteria. Overall interreader variability was assessed by Fleiss κ-statistics, and pairwise variability and intrareader reproducibility were assessed by Cohen κ-statistics. Results: For interreader variability, the readers agreed on 77% of cases (overall average agreement rate, 0.85; Fleiss κ, 0.60 [95% CI, 0.50-0.70]). The pairwise agreement rate was 0.82, 0.88, and 0.84, and the corresponding Cohen κ was 0.54 (95% CI, 0.38-0.71), 0.67 (95% CI, 0.52-0.83), and 0.59 (95% CI, 0.43-0.75), respectively. For intrareader reproducibility, the agreement rate was 0.90, 0.90, and 0.95, and the corresponding Cohen κ was 0.78 (95% CI, 0.49-0.99), 0.76 (95% CI, 0.46-0.99), and 0.89 (95% CI, 0.67-0.99), respectively. The number of actual VISION inclusion cases out of the total number of cases scored as inclusion in this substudy was 71 of 93 (agreement rate, 0.76; 95% CI, 0.66-0.85) for reader 1, 70 of 88 (0.80; 0.70-0.87) for reader 2, and 73 of 96 (0.76; 0.66-0.84) for reader 3. All readers agreed on 66 of 75 VISION inclusion cases. Conclusion: Moderate-to-substantial interreader agreement and substantial-to-almost perfect intrareader reproducibility for 68Ga-PSMA-11 PET/CT scan assessment using the VISION read criteria were observed. The read rules applied in VISION can be readily learned and demonstrate good reproducibility.

Purpose: This study aimed to investigate the characteristics of various pulmonary lesions as revealed by 68Ga-FAPI PET/CT and to determine the utility of 68Ga-FAPI PET/CT in distinguishing the nature of these pulmonary lesions. Methods: A retrospective analysis was conducted on 99 patients with pulmonary lesions, who were categorized into three distinct groups: primary lung tumors (G1), metastatic lung tumors (G2), and benign lesions (G3). Each participant underwent a 68Ga-FAPI PET/CT scan. Among these groups, variables such as the Tumor/Background Ratio (TBR), Maximum Standardized Uptake Value (SUVmax), and the true positive rate of the lesions were compared. Furthermore, the FAPI uptake in nodular-like pulmonary lesions (d<3cm) and those with irregular borders was evaluated across the groups. A correlation analysis sought to understand the relationship between FAPI uptake in primary and pulmonary metastatic lesions. Results: The study's participants were composed of 52 males and 47 females, with an average age of 56.8 ± 13.2 years. A higher uptake and detection rate for pulmonary lesions were exhibited by Group G1 compared to the other groups (SUVmax [G1 vs. G2 vs. G3: 9.1 ± 4.1 vs. 6.1 ± 4.1 vs. 5.3 ± 5.8], P<0.05; TBR [G1 vs. G2 vs. G3: 6.2 ± 2.4 vs. 4.1 ± 2.2 vs. 3.2 ± 2.7], P<0.01; true positive rate 95.1% vs. 88% vs. 75.6%]. In nodular-like lung lesions smaller than 3 cm, G1 showed a significantly higher FAPI uptake compared to G2 and G3 (SUVmax [G1 vs. G2 vs. G3: 8.8 ± 4.3 vs. 5.2 ± 3.2 vs. 4.9 ± 6.1], P<0.01; TBR [G1 vs. G2 vs. G3: 5.7 ± 2.7 vs. 3.7 ± 2.1 vs. 3.3 ± 4.4], P<0.05). Both G1 and G2 demonstrated significantly elevated FAPI agent activity in irregular-bordered pulmonary lesions when compared to G3 (SUVmax [G1 vs. G2 vs. G3: 10.9 ± 3.3 vs. 8.5 ± 2.7 vs. 4.6 ± 2.7], P<0.01; TBR [G1 vs. G2 vs. G3: 7.2 ± 2.1 vs. 6.4 ± 1.3 vs. 3.2 ± 2.4], P<0.01). A positive correlation was identified between the level of 68Ga-FAPI uptake in primary lesions and the uptake in pulmonary metastatic lesions within G2 (r=0.856, P<0.05). Conclusion: 68Ga-FAPI PET/CT imaging proves to be of significant value in the evaluation of pulmonary lesions, offering distinctive insights into their nature. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the patterns of prostate bed (PB) recurrence in prostate cancer patients experiencing prostate-specific antigen (PSA) persistence (BCP) or biochemical recurrence (BCR) after radical prostatectomy using 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET) in relation to the Radiation Therapy Oncology Group (RTOG) clinical target volumes (CTVs). Methods: This single-center, retrospective analysis included patients with BCP or BCR after radical prostatectomy and PB recurrence on 68Ga-PSMA PET. The PB recurrences were delineated by nuclear medicine physicians, the CTVs by radiation oncologists contouring guidelines on the 68Ga-PSMA PET, respectively, masked from each other. The coverage of the 68Ga-PSMA PET recurrence was categorized as PSMA recurrence completely covered, partially covered, or not covered by the RTOG-based CTV. Further, we evaluated the differences in PSMA recurrence patterns among patients with different 68Ga-PSMA PET staging (miTNM). Mann-Whitney U tests, the chi-square test, and Spearman (ρ) correlation analysis were used to investigate associations between CTV coverage and 68Ga-PSMA PET-based tumor volume, serum PSA levels, miTNM, and rectal/bladder involvement. Results: A total of 226 patients were included in the analysis; 127 patients had PSMA recurrence limited to the PB (miTrN0M0), 30 had pelvic nodal disease (miTrN1M0), 32 had extrapelvic disease (miTrN0M1), and 37 had both pelvic nodal disease and extrapelvic disease (miTrN1M1). In the miTrN0M0 cohort, the recurrence involved the rectal and bladder walls in 12 of 127 (9%) and 4 of 127 (3%), respectively. The PSMA-positive PB recurrences were completely covered by the CTV in 68 of 127 patients (53%), partially covered in 43 of 127 (34%), and not covered in 16 of 127 (13%). Full coverage was associated with a smaller tumor volume (P = 0.043), a lack of rectal/bladder wall involvement (P = 0.03), and lower miTNM staging (P = 0.035) but not with lower serum PSA levels (P = 0.979). Conclusion: Our study suggests that 68Ga-PSMA PET can be a valuable tool for guiding salvage radiation therapy (SRT) planning directed to the PB in the setting of postoperative BCR or BCP. These data should be incorporated into the redefinition of PB contouring guidelines.

Higher diagnostic accuracy, even if desirable, is not automatically associated with better outcomes. If used in settings validated with less sensitive imaging modalities, it is of paramount importance to prospectively ascertain that the higher sensitivity of prostate-specific antigen membrane-based imaging will benefit patients, and will probably not do harm.

OBJECTIVE: Long axial field-of-view (LAFOV) PET/CT showed improved performance resulting from higher sensitivity. The aim was to quantify the impact of using the full acceptance angle (UHS) in image reconstructions with the Biograph Vision Quadra LAFOV PET/CT (Siemens Healthineers) compared to the limited acceptance angle (high sensitivity mode, HS). METHODS: 38 oncological patients examined on a LAFOV Biograph Vision Quadra PET/CT were analysed. 15 patients underwent [18F]FDG-PET/CT, 15 patients underwent [18F]PSMA-1007 PET/CT, and 8 patients underwent [68Ga]Ga-DOTA-TOC PET/CT. Signal-to-noise ratio (SNR) and standardised uptake values (SUVmean/max/peak) were used to compare UHS and HS with different acquisition times. RESULTS: The SNR was significantly higher for UHS compared to HS over all acquisition times (SNR UHS/HS [18F]FDG: 1.35 ± 0.02, p

PSICHE (NCT05022914) is a prospective trial to test a [68Ga]Ga- PSMA-11 PET/CT imaging tailored strategy. All evaluable patients had biochemical relapse after surgery and underwent centralized [68Ga]Ga-PSMA-11 PET/CT imaging. The treatment was performed according pre-defined criteria. Observation and re-staging at further PSA progression were proposed to patients with negative PSMA and previous postoperative RT. Prostate bed SRT was proposed to all patients with a negative staging or positive imaging within prostate bed. Stereotactic body radiotherapy (SBRT) to all sites of disease was used for all patients with pelvic nodal recurrence (nodal disease

Here we aim to provide updated guidance and standards for the indication, acquisition, and interpretation of PSMA PET/CT for prostate cancer imaging. Procedures and characteristics are reported for a variety of available PSMA small radioligands. Different scenarios for the clinical use of PSMA-ligand PET/CT are discussed. This document provides clinicians and technicians with the best available evidence, to support the implementation of PSMA PET/CT imaging in research and routine practice.

Fibroblast-activation protein (FAP) is a serine protease classified in the dipeptidyl peptidase 4 (DPP4) family. FAP is predominantly expressed in activated fibroblasts such as the cancer-associated fibroblasts (CAFs). FAP expression in CAFs is associated with tumor progression and poor prognosis in solid cancers. Recently, radiolabeled FAP inhibitors (FAPI) has been developed, which enables positron emission tomography (PET) imaging of FAP. FAPI PET/CT can provide a higher tumor-to-background ratio (TBR) than 18F-fludeoxyglucose PET/CT in various cancers, and thus has attracted substantial attention. As studies on FAPI PET grow in number and size, incidental findings related to non-oncologic conditions have been increasingly reported. FAPI PET uptake has been reported in various conditions such as benign tumors, fibrotic, granulomatosis, scarring/wound, degenerative diseases, and inflammatory diseases.The knowledge of physiological and non-oncologic causes of FAPI uptake is indispensable for accurate FAPI PET/CT interpretation and can help appropriate management of incidental findings on FAPI PET/CT in patients referred for cancer staging indications. In this review article, we describe for each organ system (Brain, Oral mucosa, Salivary Glands, Thyroid, Lung, Myocardium, Breast, Esophagus, Stomach, Intestine, Liver, Gallbladder, Pancreas, Spleen, Kidney, , Uterus, Bone marrow, Joints, Muscle, Vessels, Lymph nodes), the patterns of physiological FAPI uptake and the main causes of non-oncological uptake reported from the literature with FAPI-02, FAPI-04 and FAPI-46. We also illustrate some examples from our institutional database at UCLA.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is a molecular and functional imaging modality with better restaging accuracy over conventional imaging for detecting prostate cancer in men suspected of lymph node (LN) progression after definitive therapy. However, the availability of PSMA PET/CT is limited in both low-resource settings and for repeating imaging surveillance. In contrast, CT is widely available, cost-effective, and routinely performed as part of patient follow-up or radiotherapy workflow. Compared with the molecular activities, the morphological and texture changes of subclinical LNs in CT are subtle, making manual detection of positive LNs infeasible. Instead, we harness the power of artificial intelligence for automated LN detection on CT. We examined 68Ga-PSMA-11 PET/CT images from 88 patients (including 739 PSMA PET/CT-positive pelvic LNs) who experienced a biochemical recurrence after radical prostatectomy and presented for salvage radiotherapy with prostate-specific antigen

Multiparametric MRI (mpMRI) is validated for the diagnosis of clinically significant prostate cancer (csPCa). 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET/CT) combined with mpMRI has improved negative predictive value over mpMRI alone for csPCa. The aim of this post hoc analysis of the PRIMARY study was to evaluate the clinical significance of patterns of intraprostatic PSMA activity, proposing a 5-point PRIMARY score to optimize the accuracy of 68Ga-PSMA PET/CT for csPCa in a low-prevalence population. Methods: The PRIMARY trial was a prospective multicenter phase II imaging trial that enrolled men with suspected PCa, no prior biopsy, and a recent mpMRI examination (6 mo) and for whom prostate biopsy was planned. In total, 291 men underwent mpMRI, 68Ga-PSMA PET/CT, and systematic biopsy with or without targeted biopsy. The mpMRI was read separately using the Prostate Imaging Reporting and Data System (PI-RADS) (version 2). 68Ga-PSMA PET/CT (pelvis only) was acquired a minimum of 60 min after injection. 68Ga-PSMA PET/CT was centrally read for pattern (diffuse transition zone [TZ], symmetric central zone [CZ], focal TZ, or focal peripheral zone [PZ]) and intensity (SUVmax). In this post hoc analysis, a 5-level PRIMARY score was assigned on the basis of analysis of the central read: no pattern (score of 1), diffuse TZ or CZ (not focal) (score of 2), focal TZ (score of 3), focal PZ (score of 4), or an SUVmax of at least 12 (score of 5). Two further readers independently assigned a PRIMARY score to 118 scans to determine interrater agreement. Associations between PRIMARY score and csPCa (International Society of Urological Pathology grade group ≥ 2) were evaluated. Results: Of the 291 men enrolled, 162 (56%) had csPCa. A PRIMARY score of 1 was present in 16% (47); a score of 2, in 19% (55); a score of 3, in 10% (29); a score of 4 in 40% (117); and a score of 5, in 15% (43). The proportion of patients with csPCa and a PRIMARY score of 1, 2, 3, 4, and 5 was 8.5% (4/47), 27% (15/55), 38% (11/29), 76% (89/117), and 100% (43/43), respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for a PRIMARY score of 1 or 2 (low-risk patterns) versus a PRIMARY score of 3-5 (high-risk patterns) were 88%, 64%, 76%, and 81%, respectively, compared with 83%, 53%, 69%, and 72%, respectively, for a PI-RADS score of 2 versus 3-5 on mpMRI. The Cohen κ for a PRIMARY score of 1 of 2 versus a PRIMARY score of 3-5 was 0.76 (95% CI, 0.64-0.88) for reader 1 and 0.64 (95% CI, 0.49-0.78) for reader 2. Conclusion: A PRIMARY score incorporating intraprostatic pattern and intensity on 68Ga-PSMA PET/CT shows potential, with high diagnostic accuracy for csPCa. Further validation is warranted before implementation.

PurposeThis study aimed to investigate the characteristics of various pulmonary lesions as revealed by 68Ga-FAPI PET/CT and to determine the utility of 68Ga-FAPI PET/CT in distinguishing the nature of these pulmonary lesions.MethodsA retrospective analysis was conducted on 99 patients with pulmonary lesions, who were categorized into three distinct groups: primary lung tumors (G1), metastatic lung tumors (G2), and benign lesions (G3). Each participant underwent a 68Ga-FAPI PET/CT scan. Among these groups, variables such as the Tumor/Background Ratio (TBR), Maximum Standardized Uptake Value (SUVmax), and the true positive rate of the lesions were compared. Furthermore, the FAPI uptake in nodular-like pulmonary lesions (d

PURPOSE: Amongst others, [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 are available for the detection of recurrent prostate cancer (rPC). There are currently limited data comparing the performance of these two radioligands with respect to clinical outcomes or their cost efficacy, which this study aims to address. METHODS: Two hundred and forty-four patients undergoing PSMA PET/CT for rPC were retrospectively analysed for this study (one hundred and twenty two with each radiopharmaceutical) to generate rates of PET positivity, negativity and unclear findings. Patients underwent follow-up to determine the rate of additional examinations and to confirm PET findings. A Markov chain decision analysis was implemented to model clinical decision-making processes and to analyse clinical performance of the two tracers. We determine their clinical cost efficacies using cost data from several countries where both radiotracers are in routine use. RESULTS: The PET positivity rate was non-significantly higher for [18F]PSMA-1007 compared to [68Ga]Ga-PSMA-11 (91.8% vs. 86.9%, p = 0.68), whereas the rate of uncertain findings was significantly greater (17.2% vs. 8.25%, p = 0.02). The probability of a true positive finding was higher for [68Ga]Ga-PSMA-11 (0.90, 95% CI 0.70-0.98) vs. [18F]PSMA-1007 (0.81, 95% CI 0.66-0.91). A significantly (p < 0.0001) higher PPV for [68Ga]Ga-PSMA-11 (0.99, 95% CI 0.99-1.0 vs. 0.86) was found compared to [18F]PSMA-1007 (0.86, 95% CI 0.82-1.00). Intervention efficacy analysis favoured [68Ga]Ga-PSMA-11, where the number needed to image (to achieve a true positive finding) was 10.58 and the number needed to image to harm (to achieve a false positive finding) was - 8.08. A cost efficacy analysis favours [68Ga]Ga-PSMA-11 in three of the four jurisdictions analysed where health economic data was available (Switzerland, Israel, Australia) and [18F]PSMA-1007 in one jurisdiction (Denmark). CONCLUSION: The analysis reveals a non-significantly higher PET positivity rate for [18F]PSMA-1007, but finds significantly greater rates of uncertain findings and false positive findings when compared to [68Ga]Ga-PSMA-11. We find differences in the two tracers in terms of clinical performance and cost efficacy. The method presented herein is generalisable and can be used with clinical or cost data for other countries or tracers.

Targeted delivery of diagnostics and therapeutics offers essential advantages over nontargeted systemic delivery. These include the reduction of toxicity, the ability to reach sites beyond biological barriers, and the delivery of higher cargo concentrations to diseased sites. Virus-like particles (VLPs) can efficiently be used for targeted delivery purposes. VLPs are derived from the coat proteins of viral capsids. They are self-assembled, biodegradable, and homogeneously distributed. In this study, hepatitis E virus (HEV) VLP derivatives, hepatitis E virus nanoparticles (HEVNPs), were radiolabeled with gallium-68, and consequently, the biodistribution of the labeled [68Ga]Ga-DOTA-HEVNPs was studied in mice. The results indicated that [68Ga]Ga-DOTA-HEVNPs can be considered as promising theranostic nanocarriers, especially for hepatocyte-targeting therapies.

Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts confer treatment resistance and promote metastasis and immunosuppression. Because FAP is overexpressed in many cancers, radiolabeled molecules targeting FAP are studied for their use as pancancer theranostic agents. This study aimed to establish the spectrum of FAP expression across various cancers by immunohistochemistry and to explore whether 68Ga FAP inhibitor (FAPi)-46 PET biodistribution faithfully reflects FAP expression from resected cancer and non-cancer specimens. Methods: We conducted a FAP expression screening using immunohistochemistry on a pancancer human tissue microarray (141 patients, 14 different types of cancer) and an interim analysis of a prospective exploratory imaging trial in cancer patients. Volunteer patients underwent 1 whole-body 68Ga-FAPi-46 PET/CT scan and, subsequently, surgical resection of their primary tumor or metastasis. 68Ga-FAPi-46 PET SUVmax and SUVmean was correlated with FAP immunohistochemistry score in cancer and tumor-adjacent non-cancer tissues for each patient. Results: FAP was expressed across all 14 cancer types on tissue microarray with variable intensity and frequency, ranging from 25% to 100% (mean, 76.6% ± 25.3%). Strong FAP expression was observed in 50%-100% of cancers of the bile duct, bladder, colon, esophagus, stomach, lung, oropharynx, ovary, and pancreas. Fifteen patients with various cancer types (colorectal [n = 4], head and neck [n = 3], pancreas [n = 2], breast [n = 2], stomach [n = 1], esophagus [n = 2], and uterus [n = 1]) underwent surgery after their 68Ga-FAPi-46 PET/CT scan within a mean interval of 16.1 ± 14.4 d. 68Ga-FAPi-46 SUVs and immunohistochemistry scores were higher in cancer than in tumor-adjacent non-cancer tissue: mean SUVmax 7.7 versus 1.6 (P

AIM: Despite increasing use for the detection of biochemically recurrent prostate cancer (rPC), the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) with [18F]PSMA-1007 remains only partially investigated. The aim of this study was to determine the sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) for PC-local recurrence and metastases on a per region basis. MATERIALS AND METHODS: One hundred seventy-seven consecutive patients undergoing [18F]PSMA-1007 PET/CT for rPC were retrospectively analysed. Six body regions were defined: prostate fossa, pelvic lymph nodes (LN), retroperitoneal LN, supradiaphragmatic LN, bones, and soft tissue. A region was counted positive if at least one PSMA-positive lesion suspicious for PC was observed. Confirmation of a true-positive PSMA-avid lesion was defined as positive by histopathology, fall in serum prostate-specific antigen (PSA) (> 50%) after targeted therapy or confirmatory further CT, MRI, PET/CT, or bone scan imaging. Regions where additional imaging was able to confirm the absence of suspicious PC lesions or regions outside exclusively targeted RT with serum PSA decline (> 50%) were counted as true-negative regions. SE, SP, PPV, and NPV were calculated for all six regions. RESULTS: The overall PET-positivity rate was 91%. Conclusive follow-up for affirmation or refutation of a PSMA-positive lesion was available for 81/152 patients on a per region basis. In this subgroup, overall sensitivity, specificity, PPV, and NPV were 95% (CI: 0.90-0.98), 89% (CI: 0.83-0.93), 86% (0.80-0.90), and 96% (CI: 0.92-0.98), respectively. On a per region basis, PPV was 97% (CI: 0.83-0.99) for local recurrence, 93% (CI: 0.78-0.98) for pelvic LN, 87% (CI: 0.62-0.96) for retroperitoneal LN, 82% (CI: 0.52-0.95) for supradiaphragmatic LN, and 79% (0.65-0.89) for bone lesions. The number of solid organ metastases (n = 6) was too small for an accurate statistical analysis. CONCLUSION: The known high PET-positivity rate of [18F]PSMA-1007 PET/CT in rPC was confirmed, with corresponding high (> 90%) sensitivity and NPV on a per region basis. However, overall PPV was limited (86%), particularly for bone lesions (79%), which are a potential diagnostic weaknesses when using this tracer.

The role of prostate-specific membrane antigen (PSMA)-targeted PET in comparison to multiparametric MRI (mpMRI) in the evaluation of intraprostatic cancer foci is not well defined. The aim of our study was to compare the diagnostic performance of 68Ga-PSMA-11 PET/CT (PSMA PET/CT), mpMRI, and PSMA PET/CT + mpMRI using 3 independent masked readers for each modality and with histopathology as the gold standard in the detection, intraprostatic localization, and determination of local extension of primary prostate cancer. Methods: Patients with intermediate- or high-risk prostate cancer who underwent PSMA PET/CT as part of a prospective trial (NCT03368547) and mpMRI before radical prostatectomy were included. Each imaging modality was interpreted by 3 independent readers who were unaware of the other modality result. A central majority rule was applied (2:1). Pathologic examination of whole-mount slices was used as the gold standard. Imaging scans and whole-mount slices were interpreted using the same standardized approach on a segment level and a lesion level. A "neighboring" approach was used to define imaging-pathology correlation for the detection of individual prostate cancer foci. Accuracy in determining the location, extraprostatic extension (EPE), and seminal vesicle invasion (SVI) of prostate cancer foci was assessed using receiver-operating-characteristic curve analysis. Interreader agreement was calculated using intraclass correlation coefficient analysis. Results: The final analysis included 74 patients (14 [19%] with intermediate risk and 60 [81%] with high risk). The cancer detection rate (lesion-based analysis) was 85%, 83%, and 87% for PSMA PET/CT, mpMRI, and PSMA PET/CT + mpMRI, respectively. The change in AUC was statistically significant between PSMA PET/CT + mpMRI and the 2 imaging modalities alone for delineation of tumor localization (segment-based analysis) (P < 0.001) but not between PSMA PET/CT and mpMRI (P = 0.093). mpMRI outperformed PSMA PET/CT in detecting EPE (P = 0.002) and SVI (P = 0.001). In the segment-level analysis, intraclass correlation coefficient analysis showed moderate reliability among PSMA PET/CT and mpMRI readers using a 5-point Likert scale (range, 0.53-0.64). In the evaluation of T staging, poor reliability was found among PSMA PET/CT readers and poor to moderate reliability was found for mpMRI readers. Conclusion: PSMA PET/CT and mpMRI have similar accuracy in the detection and intraprostatic localization of prostate cancer foci. mpMRI performs better in identifying EPE and SVI. For the T-staging evaluation of intermediate to high-risk prostate cancer, mpMRI should still be considered the imaging modality of reference. Whenever available, PSMA PET/MRI or the coregistration or fusion of PSMA PET/CT and mpMRI (PSMA PET/CT + mpMRI) should be used as it improves tumor extent delineation.

We prospectively investigated the performance of the prostate-specific membrane antigen (PSMA) ligand 68Ga-PSMA-11 for detecting prostate adenocarcinoma in patients with elevated levels of prostate-specific antigen (PSA) after initial therapy. Methods:68Ga-PSMA-11 hybrid PET was performed on 2,005 patients at the time of biochemically recurrent prostate cancer after radical prostatectomy (RP) (50.8%), definitive radiation therapy (RT) (19.7%), or RP with postoperative RT (PORT) (29.6%). The presence of prostate cancer was assessed qualitatively (detection rate = positivity rate) and quantitatively on a per-patient and per-region basis, creating a disease burden estimate from the presence or absence of local (prostate/prostate bed), nodal (N1: pelvis), and distant metastatic (M1: distant soft tissue and bone) disease. The primary study endpoint was the positive predictive value (PPV) of 68Ga-PSMA-11 PET/CT confirmed by histopathology. Results: After RP, the scan detection rate increased significantly with rising PSA level (44.8% at PSA  10 ng/mL; P

68Ga-satoreotide trizoxetan is a novel somatostatin receptor antagonist associated with high sensitivity and reproducibility in neuroendocrine tumor (NET) detection and localization. However, the optimal peptide mass and radioactivity ranges for 68Ga-satoreotide trizoxetan have not yet been established. We therefore aimed to determine its optimal dosing regimen in patients with metastatic gastroenteropancreatic NETs in a prospective, randomized, 2 × 3 factorial, multicenter phase II study. Methods: Patients received 68Ga-satoreotide trizoxetan at a peptide mass of 5-20 µg on day 1 of the study and of 30-45 µg on days 16-22, at 1 of 3 68Ga radioactivity ranges (40-80, 100-140, or 160-200 MBq). Whole-body PET/CT imaging was performed 50-70 min after each injection. The primary endpoint was the detection rate of NET lesions imaged by 68Ga-satoreotide trizoxetan relative to contrast-enhanced CT (for each of the 6 peptide mass and radioactivity range combinations). Results: Twenty-four patients were evaluated in the per-protocol analysis. The median number of lesions detected by 68Ga-satoreotide trizoxetan PET/CT or PET alone was at least twice as high as the number detected by contrast-enhanced CT across the 6 studied peptide mass and radioactivity range combinations. There were no differences between the 2 peptide mass ranges or between the 3 radioactivity ranges in the number of identified lesions. However, a trend toward a lower relative lesion count was noted in the liver for the 40- to 80-MBq range. No relationship was observed between the radioactivity range per patient's body weight (MBq/kg) and the number of lesions detected by 68Ga-satoreotide trizoxetan. The median diagnostic sensitivity of 68Ga-satoreotide trizoxetan PET/CT, based on the number of lesions per patient, ranged from 85% to 87% across the different peptide mass and radioactivity ranges. Almost all reported adverse events were mild and self-limiting. Conclusion: A radioactivity of 100-200 MBq with a peptide mass of up to 50 µg was confirmed as the optimal dosing regimen for 68Ga-satoreotide trizoxetan to be used in future phase III studies.

We aimed to systematically determine the impact of tumor burden on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent 68Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, ≤25 cm3), low (quintile 2, 25-189 cm3), moderate (quintile 3, 189-532 cm3), high (quintile 4, 532-1,355 cm3), or very high (quintile 5, ≥1,355 cm3) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using 68Ga-PSMA PET images, and SUVmean was obtained. Correlations between the SUVmean of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm3 (interquartile range [IQR], 47-1,076 cm3). The median SUVmean of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7-11.8), 26.0 (IQR, 20.0-33.4), 3.7 (IQR, 3.0-4.7), and 5.3 (IQR, 4.0-7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUVmean of the salivary glands (r = -0.44, P

PurposeFAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of 68Ga-FAPI versus standard-of-care 18F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers.Material and methodsThis international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both 68Ga-FAPI and 18F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ).ResultsA total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. 68Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for 68Ga-FAPI than 18F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, 68Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases.ConclusionQuantitative tumor uptake is comparable between 68Ga-FAPI and 18F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for 68Ga-FAPI. Thus, 68Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological 18F-FDG uptake.

In this study, we developed angiotensin-converting enzyme 2 (ACE2)-specific, peptide-derived 68Ga-labeled radiotracers, motivated by the hypotheses that ACE2 is an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and that modulation of ACE2 in coronavirus disease 2019 (COVID-19) drives severe organ injury. Methods: A series of NOTA-conjugated peptides derived from the known ACE2 inhibitor DX600 were synthesized, with variable linker identity. Since DX600 bears 2 cystine residues, both linear and cyclic peptides were studied. An ACE2 inhibition assay was used to identify lead compounds, which were labeled with 68Ga to generate peptide radiotracers (68Ga-NOTA-PEP). The aminocaproate-derived radiotracer 68Ga-NOTA-PEP4 was subsequently studied in a humanized ACE2 (hACE2) transgenic model. Results: Cyclic DX-600-derived peptides had markedly lower half-maximal inhibitory concentrations than their linear counterparts. The 3 cyclic peptides with triglycine, aminocaproate, and polyethylene glycol linkers had calculated half-maximal inhibitory concentrations similar to or lower than the parent DX600 molecule. Peptides were readily labeled with 68Ga, and the biodistribution of 68Ga-NOTA-PEP4 was determined in an hACE2 transgenic murine cohort. Pharmacologic concentrations of coadministered NOTA-PEP (blocking) showed a significant reduction of 68Ga-NOTA-PEP4 signals in the heart, liver, lungs, and small intestine. Ex vivo hACE2 activity in these organs was confirmed as a correlate to in vivo results. Conclusion: NOTA-conjugated cyclic peptides derived from the known ACE2 inhibitor DX600 retain their activity when N-conjugated for 68Ga chelation. In vivo studies in a transgenic hACE2 murine model using the lead tracer, 68Ga-NOTA-PEP4, showed specific binding in the heart, liver, lungs and intestine-organs known to be affected in SARS-CoV-2 infection. These results suggest that 68Ga-NOTA-PEP4 could be used to detect organ-specific suppression of ACE2 in SARS-CoV-2-infected murine models and COVID-19 patients.

BACKGROUND: Immune checkpoint inhibitor (ICI)-related myocarditis is a rare but potentially fatal adverse event that can occur following ICI exposure. Early diagnosis and treatment are key to improve patient outcomes. Somatostatin receptor-based positron emission tomography-CT (PET/CT) showed promising results for the assessment of myocardial inflammation, yet information regarding its value for the diagnosis of ICI-related myocarditis, especially at the early stage, is limited. Thus, we investigated the value of 68Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) PET/CT for the early detection and diagnosis of ICI-related myocarditis. METHODS: Consecutive patients with clinically suspected ICI-related myocarditis from July 2018 to February 2021 were retrospectively evaluated in this single-center study. All patients underwent imaging for the detection of ICI-related myocarditis using either cardiac magnetic resonance (CMR) imaging or 68Ga-DOTATOC PET/CT. PET/CT images were acquired 90 min after the injection of 2 MBq/kg 68Ga-DOTATOC with pathological myocardial uptake in the left ventricle (LV) suggestive of myocarditis defined using a myocardium-to-background ratio of peak standard uptake value to mean intracavitary LV standard uptake (MBRpeak) value above 1.6. Patients had a full cardiological work-up including ECG, echocardiography, serum cardiac troponin I (cTnI), cardiac troponin T and creatine kinase (CK), CK-MB. Endomyocardial biopsy and inflammatory cytokine markers were also analyzed. The detection rate of ICI-related myocarditis using 68Ga-DOTATOC PET/CT and CMR was assessed. RESULTS: A total of 11 patients had clinically suspected ICI-related myocarditis; 9 underwent 68Ga -DOTATOC PET/CT. All nine (100%) patients with 68Ga-DOTATOC PET/CT presented with pathological myocardial uptake in the LV that was suggestive of myocarditis (MBRpeak of 3.2±0.8, range 2.2-4.4). Eight patients had CMR imaging and 3/8 (38%) patients had lesions evocative of myocarditis. All PET-positive patients were previously treated with a high dose of steroids and intravenous immunoglobulin prior to PET/CT had elevated serum cTnI except for one patient for whom PET/CT was delayed several days. Interestingly, in 5/6 (83%) patients who presented with concomitant myositis, pathological uptake was seen on whole-body 68Ga-DOTATOC PET/CT images in the skeletal muscles, suggesting an additional advantage of this method to assess the full extent of the disease. In contrast, four patients with CMR imaging had negative findings despite having elevated serum cTnI levels (range 20.5-5896.1 ng/mL), thus defining possible myocarditis. Newly identified immune correlates could provide specific biomarkers for the diagnosis of ICI-related myocarditis. Most tested patients (six of seven patients) had serum increases in the inflammatory cytokine interleukin (IL)-6 and in the chemokines CXCL9, CXCL10, and CXCL13, and the mass cytometry phenotypes of immune cell populations in the blood also showed correlations with myocardial inflammation. Four of five patients with myocarditis exhibited a Th1/Th2 imbalance favoring a pronounced inflammatory Th1, Th1/Th17, and Th17 CD4 memory T-cell response. The high proportion of non-classical monocytes and significantly reduced levels of CD31 in four to five patients was also consistent with an inflammatory disease. CONCLUSION: The use of 68Ga-DOTATOC PET/CT along with immune correlates is a highly sensitive method to detect ICI-related myocarditis especially in the early stage of myocardial inflammation, as patients with elevated cTnI may present normal CMR imaging results. 68Ga-DOTATOC PET/CT is also useful for detecting concomitant myositis. These results need to be confirmed in a larger population of patients and validated against a histological gold standard if available.

OBJECTIVE: To investigate the impact of digital PET/CT on diagnostic certainty, patient-based sensitivity and interrater reliability. METHODS: Four physicians retrospectively evaluated two matched cohorts of patients undergoing [68Ga]Ga-PSMA-11 PET/CT on a digital (dPET/CT n = 65) or an analogue scanner (aPET/CT n = 65) for recurrent prostate cancer between 11/2018 and 03/2019. The number of equivocal and pathological lesions as well as the frequency of discrepant findings and the interrater reliability for the two scanners were compared. RESULTS: dPET/CT detected more lesions than aPET/CT (p < 0.001). A higher number of pathological scans were observed for dPET/CT (83% vs. 57%, p < 0.001). The true-positive rate at follow-up was 100% for dPET/CT compared to 84% for aPET/CT (p < 0.001). The proportion of lesions rated as non-pathological as a total of all PSMA-avid lesions detected for dPET/CT was comparable to aPET/CT (61.8% vs. 57.0%, p = 0.99). Neither a higher rate of diagnostically uncertain lesions (11.5% dPET/CT vs. 13.7% aPET/CT, p = 0.95) nor discrepant scans (where one or more readers differed in opinion as to whether the scan is pathological) were observed (18% dPET/CT vs. 17% aPET/CT, p = 0.76). Interrater reliability for pathological lesions was excellent for both scanner types (Cronbachs α = 0.923 dPET/CT; α = 0.948 aPET/CT) and interrater agreement was substantial for dPET/CT (Krippendorfs α = 0.701) and almost perfect in aPET/CT (α = 0.802). CONCLUSIONS: A higher detection rate for pathological lesions for dPET/CT compared with aPET/CT in multiple readers was observed. This improved sensitivity was coupled with an improved true-positive rate and was not associated with increased diagnostic uncertainty, rate of non-specific lesions, or reduced interrater reliability. KEY POINTS: • New generation digital scanners detect more cancer lesions in men with prostate cancer. • When using digital scanners, the doctors are able to diagnose prostate cancer lesions with better certainty • When using digital scanners, the doctors do not disagree with each other more than with other scanner types.

The prostate-specific membrane antigen (PSMA) has been targeted for PET imaging and radioligand therapy (RLT) in patients with prostate cancer. Xerostomia is a common side effect of RLT because of the high salivary gland uptake of PSMA radioligands. Here, we aimed to determine the impact of monosodium glutamate (MSG) administration on PSMA-radioligand biodistribution within healthy organs and tumor lesions by using 68Ga-PSMA-11 PET imaging. Methods: Sixteen men with prostate cancer were randomized (1:1) into oral ingestion and oral topical application ("swishing") arms. Each subject underwent 2 68Ga-PSMA-11 PET/CT scans within 14 d under baseline and MSG conditions. The salivary glands and whole-body tumor lesions were segmented using qPSMA software. We quantified tracer uptake via SUVmean and SUVmax and compared parameters within each patient. Results: For the oral ingestion arm, salivary gland SUVmean and SUVmax decreased on average from the control scan to the MSG scan by 45% ± 15% (P = 0.004) and 53% ± 11% (P < 0.001), respectively. Tumor lesion SUVmean and SUVmax also decreased by 38% (interquartile range, -67% to -33%) and -52% (interquartile range, -70% to -49%), respectively (P = 0.018). Swishing had no significant effect on 68Ga-PSMA-11 accumulation in normal organs or tumor lesions. Conclusion: Oral ingestion but not topical application of MSG reduced 68Ga-PSMA-11 uptake in salivary glands. Tumor uptake also declined; therefore, the clinical application of MSG is unlikely to be useful in the framework of RLT.

The purpose of this randomized trial is to evaluate the success rate of salvage radiation therapy for recurrence of prostate cancer after radical prostatectomy, with and without planning based on prostate-specific membrane antigen positron emission tomography/computed tomography. Enrollment has been completed and patients are being followed for 5yr.

The University of California Los Angeles (UCLA) and University of California San Francisco (UCSF) codeveloped 68Ga-PSMA-11 by conducting a bicentric pivotal phase 3 clinical trial for PET imaging for prostate cancer. On December 1, 2020, 2 separate new drug applications (NDAs) submitted by each institution (NDA 212642 for UCLA and NDA 212643 for UCSF) were approved by the Food and Drug Administration as the first drug for PET imaging of prostate-specific membrane antigen (PSMA)-positive lesions in men with prostate cancer. This article briefly describes the background, clinical development, regulatory approach, and regulatory process for NDA filing and approval. In the second part of this article, key chemistry, manufacturing, and controls (CMC) information is provided to facilitate abbreviated new drug application (ANDA) submission.

This work outlines the clinical implementation of total-body PET/CT from the time of installation at UC Davis EXPLORER Molecular Imaging Center in May 2019 to date (September 2020). This process has not been without challenges: logistical, technical, and medical problems were all encountered and are discussed. The mutual learning/teaching engagement among nuclear medicine technologists, research staff, radiologists, and referring physicians has been the key to the past year's achievements; these include development of ground-breaking clinical protocols for a range of Food and Drug Administration-approved radiotracers, and the attainment of a measure of expertise in clinical total-body PET/CT.

Prostate-specific membrane antigen (PSMA) ligand PET induces management changes in patients with prostate cancer. We aim to better characterize the impact of 68Ga-PSMA-11 PET (68Ga-PSMA PET) on management of recurrent prostate cancer in a large prospective cohort. Methods: We report management changes after 68Ga-PSMA PET, a secondary endpoint of a prospective multicenter trial in men with biochemical recurrence of prostate cancer. Pre-PET (Q1), post-PET (Q2), and posttreatment (Q3) questionnaires were sent to referring physicians recording site of recurrence and intended (Q1 to Q2 change) and implemented (Q3) therapeutic and diagnostic management. Results: Q1 and Q2 response was collected for 382 of 635 patients (60%, intended cohort), and Q1, Q2, and Q3 response was collected for 206 patients (32%, implemented cohort). An intended management change occurred in 260 of 382 (68%) patients. The intended change was considered major in 176 of 382 (46%) patients. Major changes occurred most often for patients with prostate-specific antigen of 0.5 to less than 2.0 ng/mL (81/147, 55%). By analysis of stage groups, management change was consistent with PET disease location, that is, a majority of major changes toward active surveillance (47%) for unknown disease site (103/382, 27%), toward local or focal therapy (56%) for locoregional disease (126/382, 33%), and toward systemic therapy (69% M1a; 43% M1b/c) for metastatic disease (153/382, 40%). According to Q3 responses, the intended management was implemented in 160 of 206 (78%) patients. In total, 150 intended diagnostic tests, mostly CT (n = 43, 29%) and bone scans or 18F-NaF PET (n = 52, 35%), were prevented by 68Ga-PSMA PET; 73 tests, mostly biopsies (n = 44, 60%) as requested by the study protocol, were triggered. Conclusion: According to referring physicians, sites of recurrence were clarified by 68Ga-PSMA PET, and disease localization translated into management changes in more than half of patients with biochemical recurrence of prostate cancer.

The impact of prostate-specific membrane antigen (PSMA) PET/CT on management of prostate cancer (PCa) patients with biochemical recurrence (BCR) is well established. However, whether and how PSMA PET/CT affects the management of patients undergoing scans for other clinical indications remains unknown. The goal of this study was to determine the impact of 68Ga-PSMA-11 PET/CT on initial and subsequent management decisions in a cohort of PCa patients referred for various indications (i.e., a basket trial) excluding the 2 main classic indications: BCR and presurgical staging. Methods: This was a prospective study of 197 patients that aimed to determine the impact of 68Ga-PSMA-11 PET/CT on PCa stage and management. The indications for PSMA PET/CT were initial staging of nonsurgical candidates (30 patients) and restaging after definitive treatment (167 patients). The restaging cohort comprised patients restaged with known advanced metastatic disease (n = 103), after androgen deprivation therapy only (n = 16), after surgery and with serum prostate-specific antigen levels lower than 0.2 ng/mL (n = 13), after radiation therapy and not meeting the Phoenix criteria (n = 22), and after other primary local treatments (i.e., high-intensity focused ultrasound, focal laser ablation, cryoablation, hyperthermia, or irreversible electroporation) (n = 13). Patients with BCR and candidates for curative surgery were excluded. Impact on management was assessed using pre- and post-PET questionnaires completed by referring physicians, electronic chart review, or patient telephone calls. Results: PSMA PET/CT changed the disease stage in 135 of 197 (69%) patients (upstaging in 38%, downstaging in 30%, and no change in stage in 32%). Management was affected in 104 of 182 (57%) patients. Specifically, PSMA PET/CT impacted the management of patients who were restaged after radiation therapy without meeting the Phoenix criteria for BCR, after other definitive local treatments, and with advanced metastatic disease in 13 of 18 (72%), 8 of 12 (67%), and 59 of 96 (61%), respectively. Conclusion: PSMA PET/CT has a profound impact on stage and management of PCa patients outside the 2 main classic indications (BCR and presurgical staging) across all examined clinical scenarios.

Our purpose was to determine the relationship between serum prostate-specific antigen (PSA) level categories (20 ng/mL) and the incidence of bone metastases detected by total-body 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT and to assess if expanding the 68Ga-PSMA-11 PET/CT imaging field to include the vertex and lower extremities (total-body acquisition) affects bone metastasis detection rates and patient management. Methods: This was a retrospective analysis of 388 prostate cancer patients enrolled in 5 prospective studies (NCT02940262, NCT03368547, NCT03042312, NCT04050215, and NCT03515577). All underwent 68Ga-PSMA-11 PET/CT scans acquired from vertex to toes for primary staging (n = 93/388, 24%), biochemical recurrence (BCR) localization (n = 225/388, 58%), or restaging metastatic disease (M1) before or during systemic therapy (n = 70/388, 18%) between September 2017 and May 2018. Results: In total, 321 of 388 patients (83%) had a positive 68Ga-PSMA-11 study. PSMA-positive bone lesions were found in 105 of 388 (27%) patients, with an incidence that was positively associated with serum PSA level (

Our purpose was to define a clinically useful lower limit of injected dose for 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT imaging of prostate cancer. Methods: 68Ga-PSMA-11 PET/CT was performed on 11 patients. PET was acquired in list mode and reconstructed using a 3-min full acquisition, a 2-min acquisition, and a 1-min acquisition to generate images obtained with three thirds (standard dose), two thirds (low dose), and one third (very low dose) of the injected dose, respectively. Overall image quality (5-point scale) was assessed, and the detectability of PSMA-positive lesions was determined by 3 readers and compared with the reference standard. Results: Image quality declined with decreasing dose (mean score of 4.1 ± 0.4 for the standard dose, 3.4 ± 0.7 for the low dose, and 1.9 ± 0.4 for the very low dose; all P < 0.05). Readers 1, 2, and 3 correctly identified the lesions (n = 21) at a rate of 100%, 100%, and 95% with the standard dose; 95%, 81%, and 90% with the low dose; and 71%, 76%, and 59% with the very low dose, respectively. Conclusion: 68Ga-PSMA-11 dose reduction is not feasible without a negative impact on image quality and lesion detectability.

PurposeThere are several important positron emission tomography (PET) imaging scenarios that require imaging with very low photon statistics, for which both quantitative accuracy and visual quality should not be neglected. For example, PET imaging with the low photon statistics is closely related to active efforts to significantly reduce radiation exposure from radiopharmaceuticals. We investigated two examples of low-count PET imaging: (a) imaging [90Y]microsphere radioembolization that suffers the very small positron emission fraction of Y-90's decay processes, and (b) cancer imaging with [68Ga]citrate with uptake time of 3-4 half-lives, necessary for visualizing tumors. In particular, we investigated a type of penalized likelihood reconstruction algorithm, block sequential regularized expectation maximization (BSREM), for improving both image quality and quantitative accuracy of these low-count PET imaging cases.ProceduresThe NEMA/IEC Body phantom filled with aqueous solution of Y-90 or Ga-68 was scanned to mimic the low-count scenarios of corresponding patient data acquisitions on a time-of-flight (TOF) PET/magnetic resonance imaging system. Contrast recovery, background variation, and signal-to-noise ratio were evaluated in different sets of count densities using both conventional TOF ordered subset expectation (TOF-OSEM) and TOF-BSREM algorithms. The regularization parameter, beta, in BSREM that controls the tradeoff between image noise and resolution was evaluated to find a value for improved confidence in image interpretation. Visual quality assessment of the images obtained from patients administered with [68Ga]citrate (n = 6) was performed. We also made preliminary visual image quality assessment for one patient with [90Y]microspheres. In Y-90 imaging, the effect of 511-keV energy window selection for minimizing the number of random events was also evaluated.ResultsQuantitatively, phantom images reconstructed with TOF-BSREM showed improved contrast recovery, background variation, and signal-to-noise ratio values over images reconstructed with TOF-OSEM. Both phantom and patient studies of delayed imaging of [68Ga]citrate show that TOF-BSREM with beta = 500 gives the best tradeoff between image noise and image resolution based on visual assessment by the readers. The NEMA-IQ phantom study with [90Y]microspheres shows that the narrow energy window (460-562 keV) recovers activity concentrations in small spheres better than the regular energy window (425-650 keV) with the beta value of 2000 using the TOF-BSREM algorithm. For the images obtained from patients with [68Ga]citrate using TOF-BSREM with beta = 500, the visual analogue scale (VAS) was improved by 17 % and the Likert score was increased by 1 point on average, both in comparison to corresponding scores for images reconstructed using TOF-OSEM.ConclusionOur investigation shows that the TOF-BSREM algorithm improves the image quality and quantitative accuracy in low-count PET imaging scenarios. However, the beta value in this algorithm needed to be adjusted for each radiopharmaceutical and counting statistics at the time of scans.

Heart failure remains a major source of late morbidity and mortality after myocardial infarction (MI). The temporospatial presence of activated fibroblasts in the injured myocardium predicts the quality of cardiac remodeling after MI. Therefore, monitoring of activated fibroblasts is of great interest for studying cardiac remodeling after MI. Fibroblast activation protein (FAP) expression is upregulated in activated fibroblasts. This study investigated the feasibility of imaging activated fibroblasts with a new 68Ga-labeled FAP inhibitor (68Ga-FAPI-04) for PET imaging of fibroblast activation in a preclinical model of MI. Methods: MI and sham-operated rats were scanned with 68Ga-FAPI-04 PET/CT (1, 3, 6, 14, 23, and 30 d after MI) and with 18F-FDG (3 d after MI). Dynamic 68Ga-FAPI-04 PET and blocking studies were performed on MI rats 7 d after coronary ligation. After in vivo scans, the animals were euthanized and their hearts harvested for ex vivo analyses. Cryosections were prepared for autoradiography, hematoxylin and eosin (H&E), and immunofluorescence staining. Results: 68Ga-FAPI-04 uptake in the injured myocardium peaked on day 6 after coronary ligation. The tracer accumulated intensely in the MI territory, as identified by decreased 18F-FDG uptake and confirmed by PET/MR and H&E staining. Autoradiography and H&E staining of cross-sections revealed that 68Ga-FAPI-04 accumulated mainly at the border zone of the infarcted myocardium. In contrast, there was only minimal uptake in the infarct of the blocked rats, comparable to the uptake in the remote noninfarcted myocardium (PET image-derived ratio of infarct uptake to remote uptake: 6 ± 2). Immunofluorescence staining confirmed the presence of FAP-positive myofibroblasts in the injured myocardium. Morphometric analysis of the whole-heart sections demonstrated 3- and 8-fold higher FAP-positive fibroblast density in the border zone than in the infarct center and remote area, respectively. Conclusion: 68Ga-FAPI-04 represents a promising radiotracer for in vivo imaging of post-MI fibroblast activation. Noninvasive imaging of activated fibroblasts may have significant diagnostic and prognostic value, which could aid clinical management of patients after MI.

Boron neutron capture therapy (BNCT) is a therapeutic modality which has been used for the treatment of cancers, including brain and head and neck tumors. For effective treatment via BNCT, efficient and selective delivery of a high boron dose to cancer cells is needed. Prostate-specific membrane antigen (PSMA) is a target for prostate cancer imaging and drug delivery. In this study, we conjugated boronic acid or carborane functional groups to a well-established PSMA inhibitor scaffold to deliver boron to prostate cancer cells and prostate tumor xenograft models. Eight boron-containing PSMA inhibitors were synthesized. All of these compounds showed a strong binding affinity to PSMA in a competition radioligand binding assay (IC50 from 555.7 to 20.3 nM). Three selected compounds 1a, 1d, and 1f were administered to mice, and their in vivo blocking of 68Ga-PSMA-11 uptake was demonstrated through a positron emission tomography (PET) imaging and biodistribution experiment. Biodistribution analysis demonstrated boron uptake of 4-7 μg/g in 22Rv1 prostate xenograft tumors and similar tumor/muscle ratios compared to the ratio for the most commonly used BNCT compound, 4-borono-l-phenylalanine (BPA). Taken together, these data suggest a potential role for PSMA targeted BNCT agents in prostate cancer therapy following suitable optimization.

BackgroundNational Comprehensive Cancer Network guidelines consider 18F-fluciclovine PET-CT for prostate cancer biochemical recurrence localisation after radical prostatectomy, whereas European Association of Urology guidelines recommend prostate-specific membrane antigen (PSMA) PET-CT. To the best of our knowledge, no prospective head-to-head comparison between these tests has been done so far. The aim of this study was to compare prospectively paired 18F-fluciclovine and PSMA PET-CT scans for localising biochemical recurrence of prostate cancer after radical prostatectomy in patients with low prostate-specific antigen (PSA) concentrations (

68Ga-PSMA-11 PET is used to stage patients with prostate cancer. We performed an updated metaanalysis that separates imaging at the time of diagnosis and at the time of biochemical recurrence and focuses on pathology correlation in both populations. Methods: We searched the MEDLINE and EMBASE databases using the PRISMA statement. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool 2. In total, 1,811 studies were screened, 58 were analyzed, 41 were included for qualitative synthesis, and 29 were included for quantitative analysis. A random-effect model and a hierarchical summary receiver-operating-characteristic model were used to summarize the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy for pelvic lymph nodes in initial staging compared with pathology at prostatectomy and the PPV for lesions with pathologic correlation in those with biochemical recurrence. We also summarized the detection rate of 68Ga-PSMA-11 in those with biochemical recurrence stratified by prostate-specific antigen (PSA) at the time of imaging. Results: The metaanalysis of 68Ga-PSMA-11 at initial staging demonstrated a sensitivity and specificity of 0.74 (95% confidence interval [95% CI], 0.51-0.89) and 0.96 (95% CI, 0.85-0.99), respectively, using nodal pathology at prostatectomy as a gold standard. At biochemical recurrence, the PPV was 0.99 (95% CI, 0.96-1.00). The detection rate was 0.63 (95% CI, 0.55-0.70), with a PSA of less than 2.0 and 0.94 (95% CI, 0.91-0.96) with a PSA of more than 2.0. Conclusion: 68Ga-PSMA-11 performed well for the localization of metastatic prostate cancer at initial staging and at the time of biochemical recurrence.

Purpose To compare the diagnostic accuracy of gallium 68 (68Ga)-labeled prostate-specific membrane antigen (PSMA)-11 PET/MRI with that of multiparametric MRI in the detection of prostate cancer. Materials and Methods The authors performed a retrospective study of men with biopsy-proven prostate cancer who underwent simultaneous 68Ga-PSMA-11 PET/MRI before radical prostatectomy between December 2015 and June 2017. The reference standard was whole-mount pathologic examination. Readers were blinded to radiologic and pathologic findings. Tumor localization was based on 30 anatomic regions. Region-specific sensitivity and specificity were calculated for PET/MRI and multiparametric MRI by using raw stringent and alternative neighboring approaches. Maximum standardized uptake value (SUVmax) in the tumor and Prostate Imaging Reporting and Data System (PI-RADS) version 2 grade were compared with tumor Gleason score. Generalized estimating equations were used to estimate population-averaged sensitivity and specificity and to determine the association between tumor characteristics and SUVmax or PI-RADS score. Results Thirty-two men (median age, 68 years; interquartile range: 62-71 years) were imaged. The region-specific sensitivities of PET/MRI and multiparametric MRI were 74% (95% confidence interval [CI]: 70%, 77%) and 50% (95% CI: 45%, 0.54%), respectively, with the alternative neighboring approach (P < .001 for both) and 73% (95% CI: 68%, 79%) and 69% (95% CI: 62%, 75%), respectively, with the population-averaged generalized estimating equation (P = .04). Region-specific specificity of PET/MRI was similar to that of multiparametric MRI with the alternative neighboring approach (88% [95% CI: 85%, 91%] vs 90% [95% CI: 87%, 92%], P = .99) and in population-averaged estimates (70% [95% CI: 64%, 76%] vs 70% [95% CI: 64%, 75%], P = .99). SUVmax was associated with a Gleason score of 7 and higher (odds ratio: 1.71 [95% CI: 1.27, 2.31], P < .001). Conclusion The sensitivity of gallium 68-labeled prostate-specific membrane antigen-11 PET/MRI in the detection of prostate cancer is better than that of multiparametric MRI. © RSNA, 2018 See also the editorial by Civelek in this issue.

Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate-specific membrane antigen (PSMA) PET/CT detects PCa metastasis with superior accuracy, having a potential impact on the planning of definitive radiation therapy (RT) for nonmetastatic PCa. Our objectives were to determine how often definitive RT planning based on standard target volumes covers 68Ga-PSMA-11 PET/CT-defined disease and to assess the potential impact of 68Ga-PSMA-11 PET/CT on definitive RT planning. Methods: This was a post hoc analysis of an intention-to-treat population of 73 patients with localized PCa without prior local therapy who underwent 68Ga-PSMA PET/CT for initial staging as part of an investigational new drug trial. Eleven of the 73 were intermediate-risk (15%), 33 were high-risk (45%), 22 were very-high-risk (30%), and 7 were N1 (9.5%). Clinical target volumes (CTVs), which included the prostate, seminal vesicles, and (in accord with the Radiation Therapy Oncology Group consensus guidelines) pelvic lymph nodes (LNs), were contoured on the CT portion of the PET/CT images by a radiation oncologist masked to the PET findings. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68Ga-PSMA-11-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had one or more 68Ga-PSMA-11-positive primary prostate lesions. Twenty-five (34%) and 7 (9.5%) of the 73 patients had 68Ga-PSMA-11-positive pelvic LN and distant metastases, respectively. The sites of LN metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper diaphragm (4%), and presacral (1.5%). The median size of the LN lesions was 6 mm (range, 4-24 mm). RT planning based on the CTVs covered 69 (94.5%) of the 73 primary lesions and 20 (80%) of the 25 pelvic LN lesions, on a per-patient analysis. Conclusion:68Ga-PSMA-11 PET/CT had a major impact on intended definitive RT planning for PCa in 12 (16.5%) of the 73 patients whose RT fields covered the prostate, seminal vesicles, and pelvic LNs and in 25 (37%) of the 66 patients whose RT fields covered the prostate and seminal vesicles but not the pelvic LNs.

PurposeSince the introduction of PSMA PET/CT with 68Ga-PSMA-11, this modality for imaging prostate cancer (PC) has spread worldwide. Preclinical studies have demonstrated that short-term androgen deprivation therapy (ADT) can significantly increase PSMA expression on PC cells. Additionally, retrospective clinical data in large patient cohorts suggest a positive association between ongoing ADT and a pathological PSMA PET/CT scan. The present evaluation was conducted to further analyse the influence of long-term ADT on PSMA PET/CT findings.MethodsA retrospective analysis was performed of all 1,704 patients who underwent a 68Ga-PSMA-11 PET/CT scan at our institution from 2011 to 2017 to detect PC. Of 306 patients scanned at least twice, 10 had started and continued ADT with a continuous clinical response between the two PSMA PET/CT scans. These ten patients were included in the current analysis which compared the tracer uptake intensity and volume of PC lesions on PSMA PET/CT before and during ongoing ADT.ResultsOverall, 31 PC lesions were visible in all ten patients before initiation of ADT. However, during ongoing ADT (duration 42-369 days, median 230 days), only 14 lesions were visible in eight of the ten patients. The average tracer uptake values decreased in 71% and increased in 12.9% of the PC lesions. Of all lesions, 33.3% were still visible in six patients with a complete PSA response (≤0.1 ng/ml).ConclusionContinuous long-term ADT significantly reduces the visibility of castration-sensitive PC on PSMA PET/CT. If the objective is visualization of the maximum possible extent of disease, we recommend referring patients for PSMA PET/CT before starting ADT.

Advanced molecular imaging has come to play an integral role in the management of gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). Somatostatin receptor (SSTR) PET has now emerged as the reference standard for the evaluation of NENs and is particularly critical in the context of peptide receptor radionuclide therapy (PRRT) eligibility. SSTR PET/MRI with liver-specific contrast agent has a strong potential for one-stop-shop multiparametric evaluation of GEP-NENs. 18F-FDG is a complementary radiotracer to SSTR, especially in the context of high-grade neuroendocrine neoplasms. Knowledge gaps in quantitative evaluation of molecular imaging studies and their role in assessment of response to PRRT and combination therapies are active research areas. Novel radiotracers have the potential to overcome existing limitations in the molecular imaging of GEP-NENs. The purpose of this article is to provide an overview of the current trends, pitfalls, and recent advancements of molecular imaging for GEP-NENs. [ABSTRACT FROM AUTHOR]

To improve prostate-specific membrane antigen (PSMA)-targeted theranostic approaches, robust murine models of prostate cancer are needed. However, important characteristics of preclinical PSMA imaging-that is, the reproducibility of the imaging signal and the relationship between quantitative cell surface PSMA expression and lesion detectability with small-animal PET/CT-have not been defined yet. Methods: Murine prostate cancer RM1 sublines (ras myc transformed cells of C57BL/6 prostate origin) expressing varying levels of human PSMA were injected into the shoulder of C57BL/6 mice on day 0. 68Ga-PSMA11 PET/CT was performed on days 7 and 8 and interpreted by 2 masked readers to determine interday and interreader reproducibility. PSMA expression was quantified on days 7 and 8 by flow cytometry of fine-needle aspiration tumor biopsy samples. Cell surface PSMA expression was correlated with PET signal. The threshold for PET positivity was based on the clinical Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria. Results: The maximum and average percentages of injected 68Ga-PSMA11 activity per gram of tissue (%IA/g) correlated nearly perfectly as determined by 2 independent readers and on 2 separate days (intraclass correlation coefficient, 1.00/0.89 and 0.95/0.88, respectively). The number of PSMA molecules per cell increased from the RM1-yellow fluorescent protein subline (PSMA-; 2,000/cell) to the RM1-low subline (PSMA+; 17,000/cell), the RM1-medium subline (PSMA++; 22,000/cell), and the RM1-PGLS subline (PSMA-positive, green fluorescent protein-positive, and luciferase-positive; PSMA+++; 45,000/cell). Expression levels correlated with the visual positivity rate on 68Ga-PSMA11 PET and with the PSMA PET %IA/g. The PSMA threshold for PET positivity was approximately 20,000 per cell. Signal correlation was close at lower PSMA levels (RM1-low to RM1-medium; 10-23 %IA/g) but was lost at higher PSMA levels (RM1-medium to RM1-PGLS; 23-27 %IA/g). Conclusion: The in vivo relationship between 68Ga-PSMA11 PET/CT and PSMA expression level in a murine model of prostate cancer was robust for lower cell surface PSMA expression levels (≤22,000/cell). Thus, preclinical 68Ga-PSMA11 PET/CT can be used as an imaging biomarker to test PSMA-targeted interventions in murine models.

In this prospective survey of referring physicians, we investigated whether and how 68Ga-labeled prostate-specific membrane antigen 11 (68Ga-PSMA-11) PET/CT affects the implemented management of prostate cancer patients with biochemical recurrence (BCR). Methods: We conducted a prospective survey of physicians (NCT02940262) who referred 161 patients with prostate cancer BCR (median prostate-specific antigen value, 1.7 ng/mL; range, 0.05-202 ng/mL). Referring physicians completed one questionnaire before the scan to indicate the treatment plan without 68Ga-PSMA-11 PET/CT information (Q1; n = 101), one immediately after the scan to denote intended management changes (Q2; n = 101), and one 3-6 mo later to document the final implemented management (Q3; n = 56). The implemented management was also obtained via electronic chart review or patient contact (n = 45). Results: A complete documented management strategy (Q1 + Q2 + implemented management) was available for 101 of 161 patients (63%). Seventy-six of these (75%) had a positive 68Ga-PSMA-11 PET/CT result. The implemented management differed from the prescan intended management (Q1) in 54 of 101 patients (53%). The postscan intended management (Q2) differed from the prescan intended management (Q1) in 62 of 101 patients (61%); however, these intended changes were not implemented in 29 of 62 patients (47%). Pelvic nodal and extrapelvic metastatic disease on 68Ga-PSMA-11 PET/CT (PSMA T0N1M0 and PSMA T0N1M1 patterns) was significantly associated with implemented management changes (P = 0.001 and 0.05). Conclusion: Information from 68Ga-PSMA-11 PET/CT brings about management changes in more than 50% of prostate cancer patients with BCR (54/101; 53%). However, intended management changes early after 68Ga-PSMA-11 PET/CT frequently differ from implemented management changes.

Target volume delineations for prostate cancer (PCa) salvage radiotherapy (SRT) after radical prostatectomy are usually drawn in the absence of visibly recurrent disease. 68Ga-labeled prostate-specific membrane antigen (PSMA-11) PET/CT detects recurrent PCa with sensitivity superior to standard-of-care imaging at serum prostate-specific antigen (PSA) values low enough to affect target volume delineations for routine SRT. Our objective was to map the recurrence pattern of PCa early biochemical recurrence (BCR) after radical prostatectomy with 68Ga-PSMA-11 PET/CT in patients with serum PSA levels of less than 1 ng/mL, determine how often consensus clinical target volumes (CTVs) based on the Radiation Therapy Oncology Group (RTOG) guidelines cover 68Ga-PSMA-11 PET/CT-defined disease, and assess the potential impact of 68Ga-PSMA-11 PET/CT on SRT. Methods: This was a post hoc analysis of an intention-to-treat population of 270 patients who underwent 68Ga-PSMA-11 PET/CT at 4 institutions for BCR after prostatectomy without prior radiotherapy at a PSA level of less than 1 ng/mL. RTOG consensus CTVs that included both the prostate bed and the pelvic lymph nodes were contoured on the CT dataset of the PET/CT image by a radiation oncologist masked to the PET component. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68Ga-PSMA-11-positive lesions not covered by planning volumes based on the consensus CTVs were considered to have a potential major impact on treatment planning. Results: The median PSA level at the time of 68Ga-PSMA-11 PET/CT was 0.48 ng/mL (range, 0.03-1 ng/mL). One hundred thirty-two of 270 patients (49%) had a positive 68Ga-PSMA-11 PET/CT result. Fifty-two of 270 (19%) had at least one PSMA-11-positive lesion not covered by the consensus CTVs. Thirty-three of 270 (12%) had extrapelvic PSMA-11-positive lesions, and 19 of 270 (7%) had PSMA-11-positive lesions within the pelvis but not covered by the consensus CTVs. The 2 most common 68Ga-PSMA-11-positive lesion locations outside the consensus CTVs were bone (23/52, 44%) and perirectal lymph nodes (16/52, 31%). Conclusion: Post hoc analysis of 68Ga-PSMA-11 PET/CT implied a major impact on SRT planning in 52 of 270 patients (19%) with PCa early BCR (PSA < 1.0 ng/mL). This finding justifies a randomized imaging trial of SRT with or without 68Ga-PSMA-11 PET/CT investigating its potential benefit on clinical outcome.

Simultaneous positron emission tomography and MRI (PET/MRI) is a technology that combines the anatomic and quantitative strengths of MR imaging with physiologic information obtained from PET. PET and computed tomography (PET/CT) performed in a single scanning session is an established technology already in widespread and accepted use worldwide. Given the higher cost and complexity of operating and interpreting the studies obtained on a PET/MRI system, there has been question as to which patients would benefit most from imaging with PET/MRI versus PET/CT. In this article, we compare PET/MRI with PET/CT, detail the applications for which PET/MRI has shown promise and discuss impediments to future adoption. It is our hope that future work will prove the benefit of PET/MRI to specific groups of patients, initially those in which PET/CT and MRI are already performed, leveraging simultaneity and allowing for greater degrees of multiparametric evaluation.Level of evidence5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1247-1262.

For prostate cancer patients who experience biochemical progression during androgen deprivation therapy (ADT), prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has not been prospectively compared to planar bone scan plus CT. This was a single-arm, head-to-head, prospective phase II trial (NCT04928820) designed to enroll 102 men with prostate cancer who experienced biochemical progression (rising prostate-specific antigen [PSA] ≥ 1 ng/mL) during ADT. All patients received 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scans. Each scan was interpreted by three central independent readers. The primary endpoint was the per-patient bone metastasis detection rate of PSMA PET/CT versus planar bone scan and CT. Secondary endpoints compared the number of bone metastases detected per patient and the inter-reader agreement of each imaging modality. Twenty-two men were enrolled between July 2021 and June 2022. Due to slow accrual following approval of PSMA PET radiotracers in the U.S. and a lack of a statistical signal between the two imaging modalities on interim analysis, this trial was closed early on October 2022. Median PSA was 8.5 ng/mL (interquartile range: 1.6-77.6). There was 100% agreement between the two scans. Six patients (27%) had negative findings and 16 patients (73%) had positive findings on both scans. PSMA PET/CT and bone scan plus CT detected an equal number of bone lesions for 14 patients (64%), PSMA PET/CT detected more bone lesions for six patients (27%), and bone scan plus CT detected more bone lesions for two patients (9.1%) (p = 0.092). The inter-reader agreement rates of PSMA PET/CT and bone scan plus CT were 96% and 82%, respectively (p = 0.25). In men with biochemical progression during ADT, 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scan plus CT had identical bone metastasis detection rates. Bone scan plus CT can continue to serve as a cost-effective and readily accessible restaging modality in patients with biochemical progression. ClinicalTrials.gov NCT04928820. Registered 16/06/2021., (© 2024. The Author(s).)

To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with 68 Ga-grazytracer, which targets granzyme B, a crucial effector molecule secreted by activated CD8 + T cells. In this phase 1/2 clinical trial (NCT05000372) involving a diverse cohort of 24 patients with solid tumors and lymphomas who received immunotherapies, including immune checkpoint inhibitors (either alone or with chemotherapies) and chimeric antigen receptor-T cell therapy, we examined the in vivo behaviors of 68 Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of 68 Ga-grazytracer, while secondary endpoint was the relationship between 68 Ga-grazytracer uptake and tumor immune phenotype. 68 Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. 68 Ga-grazytracer PET showed superior predictive value for short-term prognosis and progression-free survival than those of conventional assessment criteria, including RECIST 1.1 and PERCIST. Moreover, the uptake of 68 Ga-grazytracer in tumors was significantly higher in those with a "non-desert" immune phenotype than those with an immune "desert" phenotype, thereby meeting the primary and secondary endpoints of this trial. Collectively, we successfully visualized CD8 + T cell effector function in humans using 68 Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, patient stratification and treatment planning., (© 2024. The Author(s).)