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Objective [ 177 Lu]Lu-prostate-specific membrane antigen (PSMA)-617 radioligand therapy (RLT) shows promise for metastatic castration-resistant prostate cancer (mCRPC) patients with positive PSMA positron emission tomography (PET) imaging. Identifying high-risk patients is crucial. We evaluated pretherapeutic PSMA PET-derived parameters to predict prostate-specific antigen (PSA) response in patients undergoing [ 177 Lu]Lu-PSMA-617 RLT. Materials and Methods We conducted a retrospective analysis among 27 patients (mean age: 71.0 ± 9.5 years; range: 52–85 years) who underwent PSMA PET/computed tomography (CT) and subsequent [ 177 Lu]Lu-PSMA-617 RLT between March 2019 and January 2023. After excluding patients with liver metastases, the number of patients left for analysis was 21 (14 responders and 7 nonresponders). Tumors were semiautomatically delineated with calculation of total tumor volume (PSMA-TV), lesion uptake (PSMA-TLU = PSMA-TV * standardized uptake value [SUV]mean), and lesion quotient (PSMA-TLQ = PSMA-TV/SUVmean) for each patient. Semiquantitative parameters were analyzed only in patients with mCRPC and no liver metastasis. Results In total, 17/27 patients (62.96%) had a decline in PSA levels; 15/27 patients (55.56%) experienced a decline of > 50%. Pretherapeutic PSMA PET/CT results revealed significant differences in PSMA-TV (p = 0.003), PSMA-TLU (p = 0.013), and PSMA-TLQ (p = 0.011) between responders and nonresponders. SUVmax was significantly correlated to the best percentage change in PSA response after 177 Lu-PSMA-617 treatment (r = −0.79, p = 0.006). No association was observed between PSMA-TV (p = 0.367), PSMA-TLU (p = 0.128), and PSMA-TLQ (p = 0.556), with the best percentage change in PSA response after 177 Lu-PSMA-617 therapy. Conclusion Pretherapeutic PSMA PET-derived PSMA-TV, PSMA-TLU, and PSMA-TLQ were significant negative predictors of PSA response in patients with mCRPC and no liver metastasis receiving [ 177 Lu]Lu-PSMA-617 RLT. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop a novel positron emission tomography (PET) tracer, [68Ga]Ga-TD-01, for CXCR4 imaging. To achieve this goal, the molecular scaffold of TIQ15 was tuned by conjugation with the DOTA chelator to make it suitable for 68Ga radiolabeling. Methods: A bifunctional chelator was prepared by conjugating the amine group of TIQ15 with p-NCS-Bz-DOTA, yielding TD-01, with a high yield (68.92%). TD-01 was then radiolabeled with 68Ga using 0.1 M ammonium acetate at 60 °C for 10 min. A 1-h dynamic small animal PET/MRI study of the labeled compound in GL261-luc2 tumor-bearing mice was performed, and brain tumor uptake was assessed. Blocking studies involved pre-administration of TIQ15 (10 mg/kg) 10 min before the PET procedure started. Results: [68Ga]Ga-TD-01 exhibited a radiochemical yield (RCY) of 36.33 ± 1.50% (EOS), with a radiochemical purity > 99% and a molar activity of 55.79 ± 1.96 GBq/µmol (EOS). The radiotracer showed in vitro stability in PBS and human plasma for over 4 h. Biodistribution studies in healthy animals revealed favorable kinetics for subsequent PET pharmacokinetic modeling with low uptake in the brain and moderate uptake in lungs, intestines and spleen. Elimination could be assigned to a renal-hepatic pathway as showed by high uptake in kidneys, liver, and urinary bladder. Importantly, [68Ga]Ga-TD-01 uptake in glioblastoma (GBM)-bearing mice significantly decreased upon competition with TIQ15, with a baseline tumor-to-background ratios > 2.5 (20 min p.i.), indicating high specificity. Conclusion: The newly developed CXCR4 PET tracer, [68Ga]Ga-TD-01, exhibited a high binding inhibition for CXCR4, excellent in vitro stability, and favorable pharmacokinetics, suggesting that the compound is a promising candidate for full in vivo characterization of CXCR4 expression in GBM, with potential for further development as a tool in cancer diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic performance of 18F-fluorodeoxyglucose (18F-FDG) and 18F-fluoroestradiol (18F-FES) positron emission tomography/computed tomography (PET/CT) for initial staging of estrogen receptor (ER) positive breast cancer. Methods: Twenty-eight patients with ER-positive breast cancer underwent 18F-FDG and 18F-FES PET/CT for initial staging. Diagnostic performance and concordance rates were analyzed for both radiotracers. Semiquantitative parameters of maximum standardized uptake value (SUVmax) and tumor-to-normal ratio (T/N ratio) were compared using Wilcoxon signed-rank test. Factors potentially affecting the degree of radiotracer uptake were analyzed by multi-level linear regression analysis. Results: The overall diagnostic performance of 18F-FES was comparable to 18F-FDG, except for higher specificity and NPV, with sensitivity, specificity, PPV, NPV, and accuracy of 87.56%, 100%, 100%, 35.14%, and 88.35%, respectively, for 18F-FES and 83.94%, 30.77%, 94.74%, 11.43%, and 95.37%, respectively, for 18F-FDG. Diagnostic performance of strong ER expression was better in 18F-FES but worse for 18F-FDG. There was a correlation of mucinous cell type and Allred score 7–8 with 18F-FES uptake, with correlation coefficients of 26.65 (19.28, 34.02), 5.90 (− 0.005, 11.81), and p-value of < 0.001, 0.05, respectively. Meanwhile, luminal B and Ki-67 were related to 18F-FDG uptake, with correlation coefficients of 2.76 (1.10, 0.20), 0.11 (0.01, 0.2), and p-value of 0.018, 0.025, respectively. Conclusion: Diagnostic performance of 18F-FES is comparable to 18F-FDG, but better for strongly ER-positive breast cancer. Combination of 18F-FES and 18F-FDG would potentially overcome the limitations of each tracer with more accurate staging. [ABSTRACT FROM AUTHOR]

Background. Some studies have reported the effectiveness of [18F]PI-2620 as an effective tau-binding radiotracer; however, few reports have applied semiquantitative analysis to the tracer. Therefore, this study's aim was to perform a semiquantitative analysis of [18F]PI-2620 in individuals with normal cognition and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods. Twenty-six cognitively normal (CN) subjects, 7 patients with AD, and 36 patients with MCI were enrolled. A dynamic positron emission tomography (PET) scan was performed 30–75 min postinjection. PET and T1-weighted magnetic resonance imaging scans were coregistered. The standardized uptake value ratio (SUVr) was used for semiquantitative analysis. The P-Mod software was applied to create volumes of interest. The ANOVA and post hoc Tukey HSD were used for statistical analysis. Results. In the AD group, the occipital lobe had a significantly higher mean SUVr (1.46 ± 0.57) than in the CN and MCI groups. Compared with the CN group, the AD group showed significantly higher mean SUVr in the fusiform gyrus (1.06 ± 0.09 vs. 1.49 ± 0.86), inferior temporal (1.07 ± 0.07 vs. 1.46 ± 0.08), parietal lobe, lingual gyrus, and precuneus regions. Similarly, the AD group demonstrated a higher mean SUVr than the MCI group in the precuneus, lingual, inferior temporal, fusiform, supramarginal, orbitofrontal, and superior temporal regions. The remaining observed regions, including the striatum, basal ganglia, thalamus, and white matter, showed a low SUVr across all groups with no statistically significant differences. Conclusion. A significantly higher mean SUVr of [18F]PI-2620 was observed in the AD group; a significant area of the brain in the AD group demonstrated tau protein deposit in concordance with Braak Stages III–V, providing useful information to differentiate AD from CN and MCI. Moreover, the low SUVr in the deep striatum and thalamus could be useful for excluding primary tauopathies. [ABSTRACT FROM AUTHOR]

Objective  [ 177 Lu]Lu-prostate-specific membrane antigen (PSMA)-617 radioligand therapy (RLT) shows promise for metastatic castration-resistant prostate cancer (mCRPC) patients with positive PSMA positron emission tomography (PET) imaging. Identifying high-risk patients is crucial. We evaluated pretherapeutic PSMA PET-derived parameters to predict prostate-specific antigen (PSA) response in patients undergoing [ 177 Lu]Lu-PSMA-617 RLT. Materials and Methods  We conducted a retrospective analysis among 27 patients (mean age: 71.0 ± 9.5 years; range: 52-85 years) who underwent PSMA PET/computed tomography (CT) and subsequent [ 177 Lu]Lu-PSMA-617 RLT between March 2019 and January 2023. After excluding patients with liver metastases, the number of patients left for analysis was 21 (14 responders and 7 nonresponders). Tumors were semiautomatically delineated with calculation of total tumor volume (PSMA-TV), lesion uptake (PSMA-TLU = PSMA-TV * standardized uptake value [SUV]mean), and lesion quotient (PSMA-TLQ = PSMA-TV/SUVmean) for each patient. Semiquantitative parameters were analyzed only in patients with mCRPC and no liver metastasis. Results  In total, 17/27 patients (62.96%) had a decline in PSA levels; 15/27 patients (55.56%) experienced a decline of > 50%. Pretherapeutic PSMA PET/CT results revealed significant differences in PSMA-TV ( p  = 0.003), PSMA-TLU ( p  = 0.013), and PSMA-TLQ ( p  = 0.011) between responders and nonresponders. SUVmax was significantly correlated to the best percentage change in PSA response after 177 Lu-PSMA-617 treatment ( r  = -0.79, p  = 0.006). No association was observed between PSMA-TV ( p  = 0.367), PSMA-TLU ( p  = 0.128), and PSMA-TLQ ( p  = 0.556), with the best percentage change in PSA response after 177 Lu-PSMA-617 therapy. Conclusion  Pretherapeutic PSMA PET-derived PSMA-TV, PSMA-TLU, and PSMA-TLQ were significant negative predictors of PSA response in patients with mCRPC and no liver metastasis receiving [ 177 Lu]Lu-PSMA-617 RLT., Competing Interests: Conflict of Interest None declared., (Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

68 Ga-conjugated fibroblast activation protein inhibitor ( 68 Ga-FAPI) has become an attractive agent for PET. This study aimed to compare 68 Ga-FAPI-46 PET/CT with 18 F-FDG PET/CT for detecting primary cancer and metastatic lesions in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Twelve patients and 28 patients with HNSCC underwent 68 Ga-FAPI-46 and 18 F-FDG PET/CT for initial staging and recurrence detection, respectively. The concordance and diagnostic accuracy of both tracers were analyzed. Semiquantitative parameters, including SUV max , SUV mean , and tumor-to-background ratio, were compared. Fibroblast activation protein (FAP) expression tumor volume and total lesion FAP expression of 68 Ga-FAPI-46 were compared with metabolic tumor volume and total lesion glycolysis of 18 F-FDG, respectively. Differences between semiquantitative parameters were analyzed using paired t testing. Results: 68 Ga-FAPI-46 PET/CT was 83.3% and 96.4% concordant with 18 F-FDG PET/CT for initial staging and recurrence detection, respectively. Eighteen lesions had histopathologic validation, and both tracers displayed 100% sensitivity, 50% specificity, and 94.4% accuracy for lesion-based analysis. FAP expression tumor volume was greater than metabolic tumor volume ( P < 0.05), but no significant differences were observed for the other parameters. Conclusion: 68 Ga-FAPI-46 PET/CT showed good concordance with, and comparable diagnostic performance to, 18 F-FDG PET/CT for initial staging and recurrence detection in HNSCC patients., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)