The Homunculus of unspecific bone uptakes associated with PSMA-targeted tracers: a systematic review-based definition.

PURPOSE: Prostate-Specific Membrane Antigen (PSMA)-targeted Positron Emission Tomography (PET) has revolutionised prostate cancer (PCa) diagnosis and treatment, offering superior diagnostic accuracy over traditional methods and enabling theragnostic applications. However, a significant diagnostic challenge has emerged with identifying unspecific bone uptakes (UBUs), which could lead to over-staging and inappropriate treatment decisions if misinterpreted. This systematic review explores the phenomenon of UBUs in PCa patients undergoing PSMA-PET imaging. METHODS: Studies assessing the prevalence, topographical distribution, and potential clinical implications of UBUs were selected according to the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) method and evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. RESULTS: The percentage of PCa patients with UBUs on PSMA-PET scans ranged from 0 to 71.7%, depending on the radiopharmaceutical used, with [18F]PSMA-1007 showing the highest incidence. The ribs are the primary site of UBUs across all PSMA-targeted radiopharmaceuticals. The spine is the second most frequent UBU site for [68Ga]Ga-PSMA-11, [18F]DCFPyL, [18F]rhPSMA-7, while the pelvic girdle represents the second most frequent site for [18F]PSMA-1007. The average maximum Standardized Uptake Value (SUVmax) of UBUs varied from 3.4 to 7.7 and was generally lower than that of bone metastases. CONCLUSIONS: Our findings underscore the need for heightened awareness and precise interpretation of UBUs to avoid potential over-staging and subsequent inappropriate treatment decisions. Considering the radiopharmaceutical used, PET-derived semiquantitative parameters, the topographical distribution of UBUs, and accurately evaluating the pre-test probability based on clinical and laboratory parameters may aid nuclear medicine physicians in interpreting PSMA-PET findings.

The Diagnostic Performance of 2-[18F]FDG PET/CT in Identifying Richter Transformation in Chronic Lymphocytic Leukemia: An Updated Systematic Review and Bivariate Meta-Analysis.

Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUVmax was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95% CI: 78.5-93.3), a pooled specificity of 48.1% (95% CI: 27-69.9), a pooled negative predictive value of 90.5% (95% CI: 88.4-92.4), a pooled negative likelihood ratio of 0.35 (95% CI: 0.17-0.70), a pooled positive likelihood ratio of 1.8 (95% CI: 1.3-2.4), and a pooled diagnostic odds ratio of 6.7 (3.5-12.5) were obtained. With a higher cut-off (SUVmax = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence.

Diagnostic yield of FAP-guided positron emission tomography in thyroid cancer: a systematic review.

Background: Several recent studies have proposed the possible application of positron emission tomography/computed tomography (PET/CT) administering radiolabelled fibroblast-activation protein (FAP) inhibitors for various forms of thyroid cancer (TC), including differentiated TC (DTC), and medullary TC (MTC). Methods: The authors conducted an extensive literature search of original studies examining the effectiveness of FAP-guided PET/CT in patients with TC. The papers included were original publications exploring the use of FAP-targeted molecular imaging in restaging metastatic DTC and MTC patients. Results: A total of 6 studies concerning the diagnostic yield of FAP-targeted PET/CT in TC (274 patients, of which 247 DTC and 27 MTC) were included in this systematic review. The included articles reported high values of FAP-targeted PET/CT detection rates in TC, ranging from 81 to 100% in different anatomical sites and overall superior to the comparative imaging method. Conclusion: Although there are promising results, the existing literature on the diagnostic accuracy of FAP-guided PET in this context is still quite limited. To thoroughly evaluate its potential significance in TC patients, it is needed to conduct prospective randomized multicentric trials.

The Potential Role of PSMA-Targeted PET in Salivary Gland Malignancies: An Updated Systematic Review.

BACKGROUND: Recent studies have suggested using positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals for the detection of salivary gland malignancies (SGM), particularly adenoid-cystic carcinoma (ACC). METHODS: The authors conducted an extensive review of the scientific literature to examine the potential diagnostic role of PET/CT using PSMA-targeting radiopharmaceuticals in salivary gland malignancies (SGMs) and adenoid cystic carcinoma (ACC). This study included newly diagnosed SGM patients and those with disease recurrence in their imaging evaluation. RESULTS: This updated systematic review included a total of six studies that examined the diagnostic performance of PSMA-targeted PET/CT in ACC. The articles provided evidence of a high detection rate of PSMA-targeting PET/CT in ACC across all clinical contexts examined. SGMs other than ACC exhibited poorer diagnostic performance. CONCLUSIONS: PSMA-targeted PET/CT seems promising in detecting ACC lesions; moreover, PSMA appears to be a suitable potential target for radioligand therapy. Prospective multicentric studies are warranted to strengthen the role of PSMA-targeting radiopharmaceuticals in ACC, as both diagnostic and theragnostic agents.

Diverse Imaging Methods May Influence Long-Term Oncologic Outcomes in Oligorecurrent Prostate Cancer Patients Treated with Metastasis-Directed Therapy (the PRECISE-MDT Study).

Metastasis-directed therapy (MDT) has been tested in clinical trials as a treatment option for oligorecurrent prostate cancer (PCa). However, there is an ongoing debate regarding the impact of using different imaging techniques interchangeably for defining lesions and guiding MDT within clinical trials. Methods: We retrospectively identified oligorecurrent PCa patients who had 5 or fewer nodal, bone, or visceral metastases detected by choline or prostate-specific membrane antigen (PSMA) PET/CT and who underwent MDT stereotactic body radiotherapy with or without systemic therapy in 8 tertiary-level cancer centers. Imaging-guided MDT was assessed as progression-free survival (PFS), time to systemic treatment change due to polymetastatic conversion (PFS2), and overall survival predictor. Propensity score matching was performed to account for clinical differences between groups. Results: Of 402 patients, 232 (57.7%) and 170 (42.3%) underwent MDT guided by [18F]fluorocholine and PSMA PET/CT, respectively. After propensity score matching, patients treated with PSMA PET/CT-guided MDT demonstrated longer PFS (hazard ratio [HR], 0.49 [95% CI, 0.36-0.67]; P < 0.0001), PFS2 (HR, 0.42 [95% CI, 0.28-0.63]; P < 0.0001), and overall survival (HR, 0.39 [95% CI, 0.15-0.99]; P < 0.05) than those treated with choline PET/CT-guided MDT. Additionally, we matched patients who underwent [68Ga]Ga-PSMA-11 versus [18F]F-PSMA-1007 PET/CT, observing longer PFS and PFS2 in the former subgroup (PFS: HR, 0.51 [95% CI, 0.26-1.00]; P < 0.05; PFS2: HR, 0.24 [95% CI, 0.09-0.60]; P < 0.05). Conclusion: Diverse imaging methods may influence outcomes in oligorecurrent PCa patients undergoing MDT. However, prospective, head-to-head studies, ideally incorporating a randomized design, are necessary to provide definitive evidence and facilitate the practical application of these findings.

Diagnostic Accuracy of [68Ga]Ga Labeled Fibroblast-Activation Protein Inhibitors in Detecting Head and Neck Cancer Lesions Using Positron Emission Tomography: A Systematic Review and a Meta-Analysis.

Several studies have examined the use of positron emission tomography (PET) using [68Ga]Ga-radiolabeled fibroblast-activation protein inhibitors (FAPi) across multiple subtypes of head and neck cancer (HNC). The purpose of the present study was to evaluate the diagnostic accuracy of a newly developed molecular imaging approach in the context of HNC through a comprehensive review and meta-analysis. A thorough literature review was conducted to identify scholarly articles about the diagnostic effectiveness of FAP-targeted PET imaging. The present study incorporates original publications assessing the efficacy of this innovative molecular imaging test in both newly diagnosed and previously treated HNC patients. This systematic review examined eleven investigations, of which nine were deemed suitable for inclusion in the subsequent meta-analysis. The quantitative synthesis yielded a pooled detection rate of 99% for primary HNC lesions. Additionally, on a per patient-based analysis, the pooled sensitivity and specificity for regional lymph node metastases were found to be 90% and 84%, respectively. The analysis revealed a statistical heterogeneity among the studies for the detection rate of primary HNC lesions. The quantitative findings presented in this study indicate a favorable diagnostic performance of FAP-targeted PET imaging in detecting primary HNC tumors. In contrast, discordant results concerning the diagnostic accuracy of lymph node metastases were found. However, further multicentric trials are required to validate the efficacy of FAP-targeted PET in this specific group of patients.