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Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [177Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [177Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.

zheimer's disease (AD) causes amyloid beta (Aβ) plaque formation in regions such as the cerebral cortex and hippocampus, which have a cognitive function. Besides oxidative stress, neuroinflammation and acetylcholine, the degeneration of glutamatergic pathways in individuals with AD causes acetylcholine accumulation in the cortex and hippocampus, leading to the formation of Aβ plaque. Herein, we investigated the effects of cannabidiol (CBD) and cannabigerol (CBG) which are Cannabis sativa components on AD-like cognitive deficit induced by intracerebroventricular (icv) administration of Aβ1-42. Sprague Dawley rats were divided into four groups: i) Control, ii) Alzheimer, iii) Alzheimer+CBD, and iv) Alzheimer+CBG. The AD model was induced by icv injection of Aβ1-42 and then CBD and CBG treatments were administrated for 2 weeks. Open field test, passive avoidance test, and Morris' water maze test were performed, and on 15th day, the rats were decapitated. Hippocampus and cerebral cortex were removed from the brain, and levels of interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were measured by ELISA, and Aβ1-42 expression was evaluated immunohistochemically. There was no significant difference between the groups in the parameters evaluated by the open field test. In passive avoidance and Morris's water maze tests, both CBD and CBG enhanced the learning-memory functions impaired by AD. CBD and CBG treatments successfully reduced the levels of TNF-α and IL-1β in AD. Immunohistochemical analysis revealed decreased expression of Aβ1-42 in CBD and CBG treatment groups. CBD and CBG treatments improved learning and memory deficits in the Aβ1-42 induced AD model. We implicate that these experimental findings would lead to better avenues for targeted studies on C. sativa (a natural product of herbal origin and its components) that can potentially be developed for AD treatment. K [ABSTRACT FROM AUTHOR]

Background: The combination of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) with androgen receptor pathway inhibitors (ARPIs) has shown promise in metastatic castration-resistant prostate cancer (mCRPC). However, real-world data on the efficacy and safety of this combination are limited. This study aimed to evaluate the impact of combination therapy with Lu-177 PSMA-617 RLT and ARPIs on progression-free survival (PFS) and overall survival (OS) in patients with mCRPC. Methods: In this retrospective study, 104 mCRPC patients receiving Lu-177 PSMA-617 RLT at our institution between December 2017 and January 2024 were divided into the following two groups those receiving Lu-177 PSMA-617 RLT plus ARPI (n = 34) and those receiving Lu-177 PSMA-617 RLT alone (n = 70). Patients received 150 to 200 millicuries Lu-177 PSMA-617 RLT in each cycle. PFS and zOS were assessed using Kaplan–Meier analysis and Cox proportional hazard models. Results: The combination therapy significantly prolonged median PFS compared to Lu-177 PSMA-617 RLT alone (11 vs. 5.6 months; HR, 0.47; 95% CI, 0.28–0.79; p < 0.01). A trend towards improved OS was also observed in the combination group (20.3 vs. 15.9 months; HR, 0.58; 95% CI, 0.33–1.02; p = 0.06). Age was a significant predictor of OS (21.2 vs. 12.4 months for younger vs. older patients; p < 0.01), while Gleason score and visceral involvement did not significantly impact PFS. The safety profile indicated that adverse effects were generally comparable between the two groups, with no statistically significant differences in the incidence of anemia, neutropenia, thrombocytopenia, nephrotoxicity, or hepatotoxicity. Conclusions: This study provides evidence that combining Lu-177 PSMA-617 RLT with ARPIs may significantly improve PFS in mCRPC patients. The potential OS benefit warrants further investigation in larger prospective trials. Age should be considered when making treatment decisions for mCRPC patients. [ABSTRACT FROM AUTHOR]

Copyright of Molecular Imaging & Radionuclide Therapy is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: In our study, our aim was to investigate the role of [68 Ga]Ga-PSMA-11 PET /CT imaging in the diagnosis of clinically significant prostate cancer (csPCa) (ISUP GG 2 and higher) in patients initially diagnosed with ISUP GG 1 and 2 after prostate biopsy. Materials and methods: We retrospectively reviewed 147 patient records in whom [68 Ga]Ga-PSMA-11 PET/CT imaging was performed preoperatively. All patients were initially diagnosed with ISUP GG 1 and 2 PCa by biopsy. Final pathology reports were obtained after radical prostatectomy. The [68 Ga]Ga-PSMA-11 PET/CT images were evaluated to determine the PRIMARY score. Patients' mpMRI-PIRADS scores were also recorded when available and analyzed in correlation with the pathology results. Results: For the 114 patients scored using PRIMARY, 19 out of 37 patients with scores of 1 and 2 (51%) were diagnosed with csPCa. Of the 77 patients with PRIMARY scores between 3 and 5, 64 (83%) had csPCa. Notably, every patient with a PRIMARY score of 5 had csPCa. PRIMARY scoring had a sensitivity of 77% and specificity of 58%, with a positive predictive value of 83%. A moderate correlation was observed between PRIMARY scores and ISUP GG (Rho = 0.54, p < 0.001). In contrast, the PIRADS score displayed a sensitivity and specificity of 86% and 25% respectively, with a positive predictive value of 68%. No substantial correlation was found between PIRADS and ISUP GG. Statistical analysis revealed a significant correlation between PRIMARY and ISUP GG (p < 0.001), but not between PIRADS and ISUP GG (p = 0.281). Comparatively, PRIMARY scoring was significantly more reliable than PIRADS scoring in identifying csPCa. Conclusion: [68 Ga]Ga-PSMA-11 PET/CT imaging is promising for distinguishing high-risk prostate cancer patients from those apt for active surveillance, potentially aiding in the identification of csPCa. [ABSTRACT FROM AUTHOR]

Copyright of Molecular Imaging & Radionuclide Therapy is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)