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Understanding the relationship between lesion-absorbed dose and tumor response in 177 Lu-PSMA-617 radiopharmaceutical therapies (RPTs) remains complex. We aimed to investigate whether baseline lesion-absorbed dose can predict lesion-based responses and to explore the connection between lesion-absorbed dose and prostate-specific antigen (PSA) response. Methods: In this retrospective study, we evaluated 50 patients with 335 index lesions undergoing 177 Lu-PSMA-617 RPT, who had dosimetry analysis performed on SPECT/CT at 24 h after cycles 1 and 2. First, we identified the index lesions for each patient and measured the lesion-based absorbed doses. Lesion-based response was calculated after cycle 2. Additionally, PSA50 response (a decline of 50% from baseline PSA) after cycle 2 was also calculated. The respective responses for mean and maximum absorbed doses and prostate-specific membrane antigen (PSMA) volumetric intensity product (VIP-PSMA) at cycles 1 and 2 were termed SPECT mean , SPECT maximum , and SPECT VIP-PSMA , respectively. Results: Of the 50 patients reviewed, 46% achieved a PSA50 response after cycle 2. Of the 335 index lesions, 58% were osseous, 32% were lymph nodes, and 10% were soft-tissue metastatic lesions. The SPECT lesion-based responses were higher in PSA responders than in nonresponders (SPECT mean response of 46.8% ± 26.1% vs. 26.2% ± 24.5%, P = 0.007; SPECT maximum response of 45% ± 25.1% vs. 19% ± 27.0%, P = 0.001; SPECT VIP-PSMA response of 49.2% ± 30.3% vs. 14% ± 34.7%, P = 0.0005). An association was observed between PSA response and SPECT VIP-PSMA response ( R 2 = 0.40 and P < 0.0001). A limited relationship was found between baseline absorbed dose measured with a 24-h single time point and SPECT lesion-based response ( R 2 = 0.05, P = 0.001, and R 2 = 0.03, P = 0.007, for mean and maximum absorbed doses, respectively). Conclusion: In this retrospective study, quantitative lesion-based response correlated with patient-level PSA response. We observed a limited relationship between baseline absorbed dose and lesion-based responses. Most of the variance in response remains unexplained solely by baseline absorbed dose. Establishment of a dose-response relationship in RPT with a single time point at 24 h presented some limitations., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Fibroblast activation protein (FAP), expressed in the tumor microenvironment of a variety of cancers, has become a target of novel PET tracers. The purpose of this report is to evaluate the imaging characteristics of 68 Ga-FAP-2286, present the first-to our knowledge-dosimetry analysis to date, and compare the agent with 18 F-FDG and FAPI compounds. Methods: Patients were administered 219 ± 43 MBq of 68 Ga-FAP-2286 and scanned after 60 min. Uptake was measured in up to 5 lesions per patient and within the kidneys, spleen, liver, and mediastinum (blood pool). Absorbed doses were evaluated using MIM Encore and OLINDA/EXM version 1.1 using the International Commission on Radiological Protection publication 103 tissue weighting factor. Results: Forty-six patients were imaged with 68 Ga-FAP-2286 PET. The highest average uptake was seen in sarcoma, cholangiocarcinoma, and colon cancer. The lowest uptake was found in lung cancer and testicular cancer. The average SUV max was significantly higher on 68 Ga-FAP-2286 PET than on 18 F-FDG PET in cholangiocarcinoma (18.2 ± 6.4 vs. 9.1 ± 5.0, P = 0.007), breast cancer (11.1 ± 6.8 vs. 4.1 ± 2.2, P < 0.001), colon cancer (13.8 ± 2.2 vs. 7.6 ± 1.7, P = 0.001), hepatocellular carcinoma (9.3 ± 3.5 vs. 4.7 ± 1.3, P = 0.01), head and neck cancer (11.3 ± 3.5 vs. 7.6 ± 5.5, P = 0.04), and pancreatic adenocarcinoma (7.4 ± 1.8 vs. 3.7 ± 1.0, P = 0.01). The total-body effective dose was estimated at 1.16E-02 mSv/MBq, with the greatest absorbed organ dose in the urinary bladder wall (9.98E-02 mGy/MBq). Conclusion: 68 Ga-FAP-2286 biodistribution, dosimetry, and tumor uptake were similar to those of previously reported FAPI compounds. Additionally, 68 Ga-FAP-2286 PET had consistently higher uptake than 18 F-FDG PET. These results are especially promising in the setting of small-volume disease and differentiating tumor from inflammatory uptake., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

We report our initial real-world experience with 177 Lu-PSMA-617 radioligand therapy. Methods: We performed a retrospective review of patients treated with 177 Lu-PSMA-617. Pretreatment PSMA PET, laboratory findings, overall survival, a fall in prostate-specific antigen by 50% (PSA50), and toxicities were evaluated. Results: Ninety-nine patients were included. Sixty patients achieved a PSA50. Seven of 18 (39%) patients who did not meet the TheraP PSMA imaging criteria achieved a PSA50. Nineteen of 31 (61%) patients who did not meet the VISION laboratory criteria achieved a PSA50. Sixty-three patients had a delay or stoppage in therapy, which was due to a good response in 19 patients and progressive disease in 14 patients. Of 10 patients with a good response who restarted treatment, 9 subsequently achieved a PSA50 on retreatment. The most common toxicities were anemia (33%) and thrombocytopenia (21%). Conclusion: At our center, patients who did not meet the TheraP PSMA imaging criteria or the VISION laboratory criteria benefited from 177 Lu-PSMA-617 radioligand therapy., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Posttreatment imaging of γ-emissions after peptide receptor radionuclide therapy (PRRT) can be used to perform quantitative dosimetry as well as assessment response using qualitative measures. We aimed to assess the impact of qualitative posttreatment imaging on the management of patients undergoing PRRT. Methods: In this retrospective study, we evaluated 100 patients with advanced well-differentiated neuroendocrine tumors undergoing PRRT, who had posttreatment SPECT/CT imaging at 24 h. First, we evaluated the qualitative assessment of response at each cycle. Then using a chart review, we determined the impact on management from the posttreatment imaging. The changes in management were categorized as major or minor, and the cycles at which these changes occurred were noted. Additionally, tumor grade was also evaluated. Results: Of the 100 sequential patients reviewed, most (80% after cycle 2, 79% after cycle 3, and 73% after cycle 4) showed qualitatively stable disease during PRRT. Management changes were observed in 27% ( n = 27) of patients; 78% of those ( n = 21) were major, and 30% ( n = 9) were minor. Most treatment changes occurred after cycle 2 (33% major, 67% minor) and cycle 3 (62% major, 33% minor). Higher tumor grade correlated with increased rate of changes in management ( P = 0.006). Conclusion: In this retrospective study, qualitative analysis of posttreatment SPECT/CT imaging informed changes in management in 27% of patients. Patients with higher-grade tumors had a higher rate of change in management, and most of the management changes occurred after cycles 2 and 3. Incorporating posttreatment imaging into standard PRRT workflows could potentially enhance patient management., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose To compare quantitative measures of tumor metabolism and perfusion using fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) dedicated breast PET (dbPET) and breast dynamic contrast-enhanced (DCE) MRI during early treatment with neoadjuvant chemotherapy (NAC). Materials and Methods Prospectively collected DCE MRI and 18 F-FDG dbPET examinations were analyzed at baseline (T0) and after 3 weeks (T1) of NAC in 20 participants with 22 invasive breast cancers. FDG dbPET-derived standardized uptake value (SUV), metabolic tumor volume, and total lesion glycolysis (TLG) and MRI-derived percent enhancement (PE), signal enhancement ratio (SER), and functional tumor volume (FTV) were calculated at both time points. Differences between FDG dbPET and MRI parameters were evaluated after stratifying by receptor status, Ki-67 index, and residual cancer burden. Parameters were compared using Wilcoxon signed rank and Mann-Whitney U tests. Results High Ki-67 tumors had higher baseline SUV mean (difference, 5.1; P = .01) and SUV peak (difference, 5.5; P = .04). At T1, decreases were observed in FDG dbPET measures (pseudo-median difference T0 minus T1 value [95% CI]) of SUV max (-6.2 [-10.2, -2.6]; P < .001), SUV mean (-2.6 [-4.9, -1.3]; P < .001), SUV peak (-4.2 [-6.9, -2.3]; P < .001), and TLG (-29.1 mL 3 [-71.4, -6.8]; P = .005) and MRI measures of SER peak (-1.0 [-1.3, -0.2]; P = .02) and FTV (-11.6 mL 3 [-22.2, -1.7]; P = .009). Relative to nonresponsive tumors, responsive tumors showed a difference (95% CI) in percent change in SUV max of -34.3% (-55.9%, 1.5%; P = .06) and in PE peak of -42.4% (95% CI: -110.5%, 8.5%; P = .08). Conclusion 18 F-FDG dbPET was sensitive to early changes during NAC and provided complementary information to DCE MRI that may be useful for treatment response evaluation. Keywords: Breast, PET, Dynamic Contrast-enhanced MRI Clinical trial registration no. NCT01042379 Supplemental material is available for this article. © RSNA, 2024.

PET/CT using 16α-[ 18 F]-fluoro-17β-estradiol (FES) noninvasively images tissues expressing estrogen receptors (ERs). FES has undergone extensive clinicopathologic validation for ER+ breast cancer and received FDA approval in 2020 for clinical use as an adjunct to biopsy in patients with recurrent or metastatic ER+ breast cancer. Clinical use of FES PET/CT is increasing, but is not widespread in the United States. This AJR Expert Panel Narrative Review explores the present status and future directions of FES PET/CT, including image interpretation, existing and emerging uses, knowledge gaps, and current controversies. Specific controversies discussed include whether both FES PET/CT and FDG PET/CT are warranted in certain scenarios, whether further workup is required after negative FES PET/CT results, whether FES PET/CT findings should inform endocrine therapy selection, and whether immunohistochemistry should remain the standalone reference standard for determining ER status for all breast cancers. Consensus opinions from the panel include agreement with the appropriate clinical uses of FES PET/CT published by a multidisciplinary expert workgroup in 2023; anticipated expanded clinical use of FES PET/CT for staging ER-positive invasive lobular carcinomas and low-grade invasive ductal carcinomas pending ongoing clinical trial results; and the need for further research regarding use of FES PET/CT for ER-expressing nonbreast malignancies.

Prostate cancer is the second leading cause of cancer-related deaths in men in the United States. Imaging techniques such as CT, MRI, and bone scans have traditionally been used for diagnosis and staging. Molecular imaging modalities targeting the prostate-specific membrane antigen (PSMA) have recently gained attention due to their high affinity and accuracy. PSMA PET has been combined with other modalities such as multiparametric MRI for better diagnostic and prognostic performance. PSMA imaging has been studied at different clinical settings with a wide range of disease aggressiveness. In this review we will explore the role of PSMA PET in high-risk prostate cancer staging, biochemical recurrence, and castration-resistant prostate cancer. The primary focus of this review article is to examine the latest developments in the use of PSMA imaging and emphasize the clinical situations where its effectiveness has been demonstrated to significantly impact the treatment of prostate cancer. In addition, we will touch upon the potential future advancements of PSMA PET imaging and its evolving significance in the management of prostate cancer., (© 2023. The Author(s).)

Metabolic PET, most commonly 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT), has had a major impact on the imaging of breast cancer and can have important clinical applications in appropriate patients. While limited for screening, FDG PET/CT outperforms conventional imaging in locally advanced breast cancer. FDG PET/CT is more sensitive than conventional imaging in assessing treatment response, accurately predicting complete response or nonresponse in early-stage cases. It also aids in determining disease extent and treatment response in the metastatic setting. Further research, including randomized controlled trials with FDG and other metabolic agents such as fluciclovine, is needed for optimal breast cancer imaging., (Copyright © 2023 Elsevier Inc. All rights reserved.)

18 F-fluoroestradiol ( 18 F-FES) is a Food and Drug Administration-approved radiopharmaceutical used for molecular imaging of the estrogen receptor (ER). When combined with PET, 18 F-FES may improve the diagnosis of ER-positive breast cancer in the metastatic setting and provide insights into tumor heterogeneity. In this article, we review data on the use of 18 F-FES imaging for treatment selection, staging, imaging lobular breast cancer, and the novel breast specific imaging tool, dedicated breast PET., Competing Interests: Disclosure No disclosures for all authors included in this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The process of bringing a new drug to market is complex and has recently necessitated a new drug discovery paradigm for the pharmaceutical industry that is both more efficient and more economical. Key to this has been the increasing use of nuclear medicine and molecular imaging to support drug discovery efforts by answering critical questions on the pathway for development and approval of a new therapeutic drug. Some of these questions include: (i) Does the new drug reach its intended target in the body at sufficient levels to effectively treat or diagnose disease without unacceptable toxicity? (ii) How is the drug absorbed, metabolized, and excreted? (iii) What is the effective dose in humans? To conduct the appropriate imaging studies to answer such questions, pharmaceutical companies are increasingly partnering with molecular imaging departments. Nuclear medicine technologists are critical to this process as they perform scans to collect the qualitative and quantitative imaging data used to measure study endpoints. This article describes preclinical and clinical research trials and provides an overview of the different ways that radiopharmaceuticals are used to answer critical questions during therapeutic drug development., (Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Radionuclide therapy is a rapidly expanding oncological treatment method. Overwhelmingly, the application of radionuclide therapy in clinical practice relies on fixed or empirical dosing strategies. In principle, the application of dosimetry promises to improve patient outcomes by tailoring administered radionuclide therapy activities to each patient's unique tumour burden and tumour uptake. However, robust prospective data are scarce due to few prospective randomised clinical trials investigating the use of dosimetry in radionuclide therapy. In this Review, we describe the role of dosimetry as it has been applied historically and in modern clinical practice and its potential future applications. We further emphasise areas of future growth and a potential pathway to optimised personalised activity modulation of radionuclide therapy., Competing Interests: Declaration of interests TAH declares research grants from Clovis Oncology and AAA/Novartis; consulting fees from Curium, Ipsen, and Blue Earth Diagnostics; a leadership role in the North American Neuroendocrine Tumor Society; and stock or stock options in RayzeBio, a radiopharmaceuticals company. EKF declares consulting fees for dosimetry from Invicro and Ymabs. RRF declares a research grant from the US Department of Defense Prostate Cancer Research Program on radionuclide therapy development. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: 18 F-Fluciclovine PET imaging has been increasingly used in the restaging of prostate cancer patients with biochemical recurrence (BCR); however, its clinical utility in patients with low prostate-specific antigen (PSA) levels following primary radiation therapy has not been well-studied. This study aims to determine the detection rate and diagnostic accuracy of 18 F-fluciclovine PET and the patterns of prostate cancer recurrence in patients with rising PSA after initial radiation therapy, particularly in patients with PSA levels below the accepted Phoenix definition of BCR (PSA nadir +2 ng/mL)., Methods: This retrospective study included patients from two tertiary institutions who underwent 18 F-fluciclovine PET scans for elevated PSA level following initial external beam radiation therapy, brachytherapy, and/or proton therapy. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic accuracy of 18 F-fluciclovine PET and associations of PSA kinetic parameters with 18 F-fluciclovine PET outcome., Results: One hundred patients were included in this study. The overall detection rate on a patient-level was 79% (79/100). 18 F-Fluciclovine PET was positive in 62% (23/37) of cases with PSA below the Phoenix criteria. The positive predictive value of 18 F-fluciclovine PET was 89% (95% CI: 80-94%). In patients with PSA below the Phoenix criteria, the PSA velocity had the highest predictive value of 18 F-fluciclovine PET outcome. PSA doubling time (PSADT) and PSA velocity were associated with the presence of extra-pelvic metastatic disease., Conclusion: 18 F-Fluciclovine PET can identify recurrent disease at low PSA level and PSA rise below accepted Phoenix criteria in patients with suspected BCR after primary radiation therapy, particularly in patients with low PSADT or high PSA velocity. In patients with low PSADT or high PSA velocity, there is an increased probability of extra-pelvic metastases. Therefore, these patients are more likely to benefit from PET/CT or PET/MRI than pelvic MRI alone., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: The presence of pelvic nodal metastases at radical prostatectomy is associated with biochemical recurrence after prostatectomy., Objective: To assess the accuracy of prostate-specific membrane antigen (PSMA) 68Ga-PSMA-11 positron emission tomographic (PET) imaging for the detection of pelvic nodal metastases compared with histopathology at time of radical prostatectomy and pelvic lymph node dissection., Design, Setting, and Participants: This investigator-initiated prospective multicenter single-arm open-label phase 3 imaging trial of diagnostic efficacy enrolled 764 patients with intermediate- to high-risk prostate cancer considered for prostatectomy at University of California, San Francisco and University of California, Los Angeles from December 2015 to December 2019. Data analysis took place from October 2018 to July 2021., Interventions: Imaging scan with 3 to 7 mCi of 68Ga-PSMA-11 PET., Main Outcomes and Measures: The primary end point was the sensitivity and specificity for the detection pelvic lymph nodes compared with histopathology on a per-patient basis using nodal region correlation. Each scan was read centrally by 3 blinded independent central readers, and a majority rule was used for analysis., Results: A total of 764 men (median [interquartile range] age, 69 [63-73] years) underwent 1 68Ga-PSMA-11 PET imaging scan for primary staging, and 277 of 764 (36%) subsequently underwent prostatectomy with lymph node dissection (efficacy analysis cohort). Based on pathology reports, 75 of 277 patients (27%) had pelvic nodal metastasis. Results of 68Ga-PSMA-11 PET were positive in 40 of 277 (14%), 2 of 277 (1%), and 7 of 277 (3%) of patients for pelvic nodal, extrapelvic nodal, and bone metastatic disease. Sensitivity, specificity, positive predictive value, and negative predictive value for pelvic nodal metastases were 0.40 (95% CI, 0.34-0.46), 0.95 (95% CI, 0.92-0.97), 0.75 (95% CI, 0.70-0.80), and 0.81 (95% CI, 0.76-0.85), respectively. Of the 764 patients, 487 (64%) did not undergo prostatectomy, of which 108 were lost to follow-up. Patients with follow-up instead underwent radiotherapy (262 of 379 [69%]), systemic therapy (82 of 379 [22%]), surveillance (16 of 379 [4%]), or other treatments (19 of 379 [5%])., Conclusions and Relevance: This phase 3 diagnostic efficacy trial found that in men with intermediate- to high-risk prostate cancer who underwent radical prostatectomy and lymph node dissection, the sensitivity and specificity of 68Ga-PSMA-11 PET were 0.40 and 0.95, respectively. This academic collaboration is the largest known to date and formed the foundation of a New Drug Application for 68Ga-PSMA-11., Trial Registration: ClinicalTrials.gov Identifiers: NCT03368547, NCT02611882, and NCT02919111.

Background: Neuroendocrine neoplasms (NENs) comprise a rare and heterogenous group of cancers, for which the role of radiation therapy continues to evolve. The purpose of this study is to analyze oncologic outcomes after the use of high-dose radiation in management of NENs at a tertiary hospital., Materials and Methods: We performed a retrospective review of patients who received high-dose radiation with intent to cure or provide durable local control (defined as biologically effective dose (BED) ≥40, α/β = 10) for a localized or metastatic NEN from 2006 to 2019. Evaluation of disease status after radiation was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria when possible. Patients were grouped by differentiation (well-differentiated (WD) or poorly-differentiated (PD)) and stage (localized/locally advanced disease (L) or metastatic (M)) in analysis of probabilities of progression after radiation., Results: 45 patients completed a radiation course with BED ≥40 for a NEN (median BED 72). With a median follow-up of 24 months after radiation, the 2-year actuarial rates of local relapse-free survival, new metastasis-free survival, progression-free survival, and overall survival after radiation were 98%, 45%, 41%, and 69%, respectively. 25 patients (56%) developed new metastases after completion of radiation, including 33% (n = 3) of patients with WD-L disease, 44% (n = 8) of WD-M, 77% (n = 10) of PD-L, and 80% (n = 4) of PD-M, with progressively shorter median times to progression (26, 9, 8, and 3 months, respectively; p = 0.093). Of the 25 patients evaluable by RECIST, 68% (n = 17) achieved either a complete or partial best response in the irradiated lesion., Conclusions: These data suggest that focal, high-dose radiation has a role in the management of selected patients with NENs. Local failure is rare in patients with both well-differentiated and poorly-differentiated disease, although the predominant pattern of failure remains development of new metastases., Competing Interests: The authors have declared that no competing interests exist.

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals are playing a large role at the time of initial staging and biochemical recurrence for localizing prostate cancer, as well as in other emerging clinical settings. PSMA PET has demonstrated increased detection rate compared with conventional imaging and has been shown to change management plans in a substantial percentage of cases. The aims of this narrative review are to highlight the development and clinical impact of PSMA PET radiopharmaceuticals, to compare PSMA to other agents such as fluorine 18 fluciclovine and carbon 11 choline, and to highlight some of the individual PSMA PET agents that have contributed to the advancement of prostate cancer imaging., (© RSNA, 2021 See also the editorial by Jadvar in this issue.)

Purpose: Readers need to be informed about potential pitfalls of [ 68 Ga]Ga-PSMA-11 PET interpretation., Methods: Here we report [ 68 Ga]Ga-PSMA-11 PET findings discordant with the histopathology/composite reference standard in a recently published prospective trial on 635 patients with biochemically recurrent prostate cancer., Results: Consensus reads were false positive in 20 regions of 17/217 (8%) patients with lesion validation. Majority of the false positive interpretations (13 of 20, 65%) occurred in the context of suspected prostate (bed) relapse (T) after radiotherapy (n = 11); other false positive findings were noted for prostate bed post prostatectomy (T, n = 2), pelvic nodes (N, n = 2), or extra pelvic lesions (M, n = 5). Major sources of false positive findings were PSMA-expressing residual adenocarcinoma with marked post-radiotherapy treatment effect. False negative interpretation occurred in 8 regions of 6/79 (8%) patients with histopathology validation, including prostate (bed) (n = 5), pelvic nodes (n = 1), and extra pelvic lesions (n = 2). Lesions were missed mostly due to small metastases or adjacent bladder/urine uptake., Conclusion: [ 68 Ga]Ga-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of [ 68 Ga]Ga-PSMA-11 PET false positivity. In few cases, PET correctly detects residual PSMA expression post-radiotherapy, originating however from treated, benign tissue or potentially indolent tumor remnants., Trial Registration Number: ClinicalTrials.gov Identifiers: NCT02940262 and NCT03353740.

Given the high frequency of liver metastases in neuroendocrine tumor patients, we aimed to determine whether hepatic intraarterial administration of 90 Y-DOTATOC peptide receptor radionuclide therapy (PRRT) would increase treatment efficacy while reducing systemic toxicity compared with systemic toxicity from intravenous administration as previously reported in the literature. Methods: PRRT-naïve adult neuroendocrine tumor patients with liver-dominant metastases were enrolled in a prospective single-center, open-label pilot study. The patients underwent baseline PET/CT using intravenous 68 Ga-DOTATOC. Then, 3.5 ± 0.2 GBq (94.7 ± 5.4 mCi) of 90 Y-DOTATOC were administered into the proper hepatic artery over 30 min. The first 5 patients also received intraarterial 68 Ga-DOTATOC and underwent PET/CT. All patients were followed for response (RECIST, version 1.1) (primary aim 2, safety) and toxicity (Common Terminology Criteria for Adverse Events, version 4.0) (primary aim 1, efficacy) for at least 6 mo, with optional follow-up for up to 1 y. In the subset of 5 patients who underwent both intravenous and intraarterial 68 Ga-DOTATOC PET/CT, tumor SUV max was compared between intravenous and intraarterial administration for hepatic tumors, intrahepatic tumors, and uninvolved background organs (secondary aim, intravenous vs. intraarterial uptake). Results: The study was terminated after a planned analysis of the first 10 patients because of lack of efficacy. The best response was stable disease in 90% (9/10 patients) and progressive disease in 10% (1/10 patients) at 3 mo, and stable disease in 8 of 10 patients and progressive disease in 2 of 10 patients at 6 mo. One additional patient developed progressive disease after the 6-mo follow-up period but within the optional 1-y follow-up period. No partial response or complete response was observed. The 2 patients with the highest liver tumor burden died within 6 mo of treatment, with treatment considered a possible contributor. Patients who received intraarterial administration failed to demonstrate higher uptake by hepatic metastases than patients who received intravenous administration, with a median intraarterial-to-intravenous SUV max ratio of 0.81 (range, 0.36-2.09) on a lesion level. Conclusion: Our study found that administration of PRRT via the proper hepatic artery did not reproduce the increase in hepatic tumor uptake that was previously reported. In addition, the single treatment using 90 Y-DOTATOC did not induce tumor shrinkage, indicating that more treatment cycles may be required. Possible safety concerns in patients with a high liver tumor burden should inform patient selection for future studies., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Prostate-specific membrane antigen (PSMA) ligand PET induces management changes in patients with prostate cancer. We aim to better characterize the impact of 68 Ga-PSMA-11 PET ( 68 Ga-PSMA PET) on management of recurrent prostate cancer in a large prospective cohort. Methods: We report management changes after 68 Ga-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 18 F-NaF PET ( n = 52, 35%), were prevented by 68 Ga-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 68 Ga-PSMA PET, and disease localization translated into management changes in more than half of patients with biochemical recurrence of prostate cancer., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Bone is the most common site of distant metastatic spread in prostate adenocarcinoma. Prostate-specific membrane antigen (PSMA) uptake has been described in both benign and malignant bone lesions, which can lead to false-positive findings on 68 Ga-PSMA-11 PET. The purpose of this study was to evaluate the diagnostic accuracy of 68 Ga-PSMA-11 PET for osseous prostate cancer metastases and improve bone uptake interpretation using semiquantitative metrics. Methods: Fifty-six prostate cancer patients (18 before prostatectomy and 38 with biochemical recurrence) who underwent 68 Ga-PSMA-11 PET/MRI or PET/CT examinations with osseous PSMA-ligand uptake were included in the study. Medical records were reviewed retrospectively by board-certified nuclear radiologists to determine true or false positivity based on a composite endpoint. For each avid osseous lesion, we measured biologic volume; size; PSMA Reporting and Data System (RADS) rating; SUV max ; and ratio of lesion SUV max to liver, blood pool, and background bone SUV max Differences between benign and malignant lesions were evaluated for statistical significance, and cutoffs for these parameters were determined to maximize diagnostic accuracy. Results: Among 56 participants, 13 (22.8%) had false-positive osseous 68 Ga-PSMA-11 findings and 43 (76.8%) had true-positive osseous 68 Ga-PSMA-11 findings. Twenty-two patients (39%) had 1 osseous lesion, 18 (32%) had 2-4 lesions, and 16 (29%) had 5 or more lesions. Cutoffs resulting in statistically significant ( P < 0.005) differences between benign and malignant lesions were a PSMA RADS rating of at least 4, an SUV max of at least 4.1, and SUV max ratios of at least 2.11 for lesion to blood pool, at least 0.55 for lesion to liver, and at least 4.4 for lesion to bone. These measurements corresponded to a lesion-based 68 Ga-PSMA-11 PET lesion detection rate of 80%, 93%, 89%, 21%, and 89%, respectively, for malignancy, and a specificity of 73%, 73%, 73%, 93%, and 60%, respectively. Conclusion: PSMA RADS rating, SUV max , and SUV max ratio for lesion to blood pool can help differentiate benign from malignant lesions on 68 Ga-PSMA-11 PET. An SUV max ratio of more than 2.2 for lesion to blood pool is a reasonable parameter to support image interpretation and presented a superior lesion detection rate and specificity when compared with visual interpretation by PSMA RADS. These parameters hold clinical value by improving diagnostic accuracy for metastatic prostate cancer on 68 Ga-PSMA-11 PET/MRI and PET/CT., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Prostate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [ 68 Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients., Methods: Eligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[ 18 F]FDG PET and/or 131 I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [ 68 Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[ 18 F]FDG PET CT/MRI for lesion location and relative intensity., Results: Twelve patients underwent [ 68 Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[ 18 F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[ 18 F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype., Conclusions: [ 68 Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[ 18 F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.

OBJECTIVE. The purpose of this study was to determine the diagnostic accuracy of 68 Ga-labeled prostate-specific membrane antigen 11 (PSMA-11) PET for disease detection in patients with prostate cancer who have biochemically recurrent disease after radiation therapy or prostatectomy. SUBJECTS AND METHODS. One hundred fifty patients underwent 68 Ga-PSMA-11 PET/CT or PET/MRI, and the images were interpreted by two blinded board-certified radiologists. Each reader evaluated for the presence or absence of PSMA-positive disease within the prostate bed, pelvic lymph nodes, bones, and soft tissues (extrapelvic lymph nodes and visceral structures). The presence or absence of disease was confirmed by histopathologic analysis if available. For patients who did not have pathologic analysis, a composite of imaging and clinical follow-up was used as the reference standard. RESULTS. The median prostate-specific antigen level was 2.1 ng/mL. Forty-three patients had pathologic correlation, and for 29 patients a composite of imaging and follow-up was used to determine the presence or absence of disease. With substantial to almost perfect interreader reliability by region (κ = 0.78-0.87), 68 Ga-PSMA-11 PET had high sensitivity per region (up to 100%) and per patient (up to 89.8%). It also had high positive predictive value per region (up to 100%) and per patient (up to 91.5%). Sensitivity was highest for bone metastases and lowest for soft-tissue metastases. Positive predictive value was highest for bone metastases and lowest for prostate bed recurrence. CONCLUSION. Gallium-68-labeled PSMA-11 PET is sensitive for prostate cancer metastases in patients with biochemically recurrent prostate cancer. It has high positive predictive value and substantial to almost perfect interrater reliability.

Objective: The purpose of this article is to describe the large number of radiotracers being evaluated for prostate-specific membrane antigen (PSMA) PET, which is becoming a central tool in the staging of prostate cancer., Conclusion: PSMA PET is a highly promising modality for the staging of prostate cancer because of its higher detection rate compared with that of conventional imaging. Both PET/CT and PET/MRI offer benefits with PSMA radiotracers, and PSMA PET findings frequently lead to changes in management. It is imperative that subsequent treatment changes be evaluated to show improved outcomes. PSMA PET also has potential applications, including patient selection for PSMA-based radioligand therapy and evaluation of treatment response.

Purpose: To assess the utility of furosemide diuresis and the role of an improved scatter correction algorithm in reducing scatter artifact severity on Ga-68- Prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)., Materials and Methods: A total of 139 patients underwent Ga-68-PSMA-11 PET imaging for prostate cancer: 47 non-time-of-flight (non-TOF) PET/computed tomography, 51 PET/magnetic resonance imaging (MRI) using the standard TOF scatter correction algorithm, and 41 PET/MRI using an improved TOF scatter correction algorithm. Whole-body PET acquisitions were subdivided into 3 regions: around kidneys; between kidneys and bladder; and around bladder. The images were reviewed, and scatter artifact severity was rated using a Likert-type scale., Results: The worst scatter occurred when using non-TOF scatter correction without furosemide, where 42.1% of patients demonstrated severe scatter artifacts in 1 or more regions. Improved TOF scatter correction resulted in the smallest percentage of studies with severe scatter (6.5%). Scatter ratings by region were lowest using improved TOF scatter correction. Furosemide reduced mean scatter severity when using non-TOF and standard TOF., Conclusions: Both furosemide and scatter correction algorithm play a role in reducing scatter in PSMA PET. Improved TOF scatter correction resulted in the lowest scatter severity.

We present a case of an incidentally detected squamous cell carcinoma of the oropharynx on Ga-PSMA-11 PET. A 71-year-old man's condition was diagnosed as prostate carcinoma after a year of rising serum prostate-specific antigen. The staging Ga-PSMA PET/CT demonstrated focal radiotracer uptake in the prostate corresponding to his known primary prostate cancer. However, a PSMA-avid 3.4-cm mass was incidentally found in the right tongue base that was biopsied, confirming squamous cell carcinoma.

Acute dizziness (including vertigo) is a common reason to visit the emergency room, and imaging with head CT is often performed initially to exclude a central cause. In this study, consecutive patients presenting with dizziness and undergoing head CT were retrospectively reviewed to determine diagnostic yield. Four hundred forty-eight consecutive head CTs in a representative sample of dizzy emergency room (ER) patients, including patients with other neurological symptoms, were reviewed to identify an acute or subacute cause for acute dizziness along with the frequency and modalities used in follow-up imaging. The diagnostic yield for head CT ordered in the ER for acute dizziness is low (2.2 %; 1.6 % for emergent findings), but MRI changes the diagnosis up to 16 % of the time, acutely in 8 % of cases. Consistent with the American College of Radiology appropriateness criteria and the literature, this study suggests a low diagnostic yield for CT in the evaluation of acute dizziness but an important role for MRI in appropriately selected cases.

Purpose: The DBA/2J mice have been used as an animal model for human pigmentary glaucoma. However, these mice develop various degrees of disease symptoms at different ages, making it difficult to detect pathological changes of retinal degeneration at glaucoma onset. The purpose of this study is to develop a non-invasive assay to identify individual mice that develop visual deficits., Materials and Methods: We apply two behavioral tests, a swimming test of visual discrimination and a test of optomotor response, to identify glaucomatous DBA/2J mice. We then examine whether the elevation of intraocular pressure (IOP), the common risk factor for glaucoma, affects visual performances of the DBA/2J mice. We further compare the retinal ganglion cell death, one of the signature glaucoma symptoms, in mice with normal behavior with those with poor visual performances., Results: Our data demonstrate that (1) the onset of visual deficits in DBA/2J mice is around 7 months of age; (2) within each age group, there are various degrees of visual deficits; and (3) the percentage of mice exhibiting visual deficits increases with age and their visual capacities decrease gradually. Furthermore, the poor visual performances of DBA/2J mice do not correlate with the elevation of IOP. Importantly, compared to mice with normal visual performances in the same age group, mice with poor visual performances exhibit significant loss of retinal ganglion cells., Conclusions: Our studies establish a reliable behavioral assay to identify glaucomatous DBA/2J mice, thus making it possible to examine subtle pathological changes and molecular mechanisms in glaucoma pathogenesis with a relatively small number of samples.