Journal of Nuclear Medicine最新文献

Glypican-1 (GPC1) is overexpressed in several solid cancers and is associated with tumor progression, whereas its expression is low in normal tissues. This study aimed to evaluate the potential of an anti-GPC1 monoclonal antibody (GPC1 mAb) labeled with ⁸⁹Zr or ²¹¹At as a theranostic target in pancreatic ductal adenocarcinoma. Methods: GPC1 mAb clone 01a033 was labeled with ⁸⁹Zr or ²¹¹At with a deferoxamine or decaborane linker, respectively. The internalization ability of GPC1 mAb was evaluated by fluorescence conjugation using a confocal microscope. PANC-1 xenograft mice (n = 6) were intravenously administered [⁸⁹Zr]GPC1 mAb (0.91 ± 0.10 MBq), and PET/CT scanning was performed for 7 d. Uptake specificity was confirmed through a comparative study using GPC1-positive (BxPC-3) and GPC1-negative (BxPC-3 GPC1-knockout) xenografts (each n = 3) and a blocking study. DNA double-strand breaks were evaluated using the γH2AX antibody. The antitumor effect was evaluated by administering [²¹¹At]GPC1 mAb (∼100 kBq) to PANC-1 xenograft mice (n = 10). Results: GPC1 mAb clone 01a033 showed increased internalization ratios over time. One day after administration, a high accumulation of [⁸⁹Zr]GPC1 mAb was observed in the PANC-1 xenograft (SUV_max, 3.85 ± 0.10), which gradually decreased until day 7 (SUV_max, 2.16 ± 0.30). The uptake in the BxPC-3 xenograft was significantly higher than in the BxPC-3 GPC1-knockout xenograft (SUV_max, 4.66 ± 0.40 and 2.36 ± 0.36, respectively; P = 0.05). The uptake was significantly inhibited in the blocking group compared with the nonblocking group (percentage injected dose per gram, 7.3 ± 1.3 and 12.4 ± 3.0, respectively; P = 0.05). DNA double-strand breaks were observed by adding 150 kBq of [²¹¹At]GPC1 and were significantly suppressed by the internalization inhibitor (dynasore), suggesting a substantial contribution of the internalization ability to the antitumor effect. Tumor growth suppression was observed in PANC-1 mice after the administration of [²¹¹At]GPC1 mAb. Internalization inhibitors (prochlorperazine) significantly inhibited the therapeutic effect of [²¹¹At]GPC1 mAb, suggesting an essential role in targeted α-therapy. Conclusion: [⁸⁹Zr]GPC1 mAb PET showed high tumoral uptake in the early phase after administration, and targeted α-therapy using [²¹¹At]GPC1 mAb showed tumor growth suppression. GPC1 is a promising target for future applications for the precise diagnosis of pancreatic ductal adenocarcinoma and GPC1-targeted theranostics.

We evaluated whether the artificial intelligence chatbot ChatGPT can adequately answer patient questions related to [¹⁸F]FDG PET/CT in common clinical indications before and after scanning. Methods: Thirteen questions regarding [¹⁸F]FDG PET/CT were submitted to ChatGPT. ChatGPT was also asked to explain 6 PET/CT reports (lung cancer, Hodgkin lymphoma) and answer 6 follow-up questions (e.g., on tumor stage or recommended treatment). To be rated "useful" or "appropriate," a response had to be adequate by the standards of the nuclear medicine staff. Inconsistency was assessed by regenerating responses. Results: Responses were rated "appropriate" for 92% of 25 tasks and "useful" for 96%. Considerable inconsistencies were found between regenerated responses for 16% of tasks. Responses to 83% of sensitive questions (e.g., staging/treatment options) were rated "empathetic." Conclusion: ChatGPT might adequately substitute for advice given to patients by nuclear medicine staff in the investigated settings. Improving the consistency of ChatGPT would further increase reliability.

²²³Ra-dichloride (²²³Ra) and ¹⁷⁷Lu-prostate-specific membrane antigen (PSMA) are approved treatments for metastatic castration-resistant prostate cancer (mCRPC). The safety and effectiveness of sequential use of ²²³Ra and ¹⁷⁷Lu-PSMA in patients with mCRPC are not well described. This study aimed to evaluate ¹⁷⁷Lu-PSMA safety and efficacy in patients with mCRPC previously treated with ²²³Ra. Methods: The radium→lutetium (RALU) study was a multicenter, retrospective, medical chart review. Participants had received at least 1 ²²³Ra dose and, in any subsequent therapy line, at least 1 ¹⁷⁷Lu-PSMA dose. Primary endpoints included the incidence of adverse events (AEs), serious AEs, grade 3-4 hematologic AEs, and abnormal laboratory values. Secondary endpoints included overall survival, time to next treatment/death, and change from baseline in serum prostate-specific antigen and alkaline phosphatase levels. Results: Data were from 133 patients. Before ¹⁷⁷Lu-PSMA therapy, 56% (75/133) of patients received at least 4 life-prolonging therapies; all patients received ²²³Ra (73% received 5-6 injections). Overall, 27% (36/133) of patients received at least 5 ¹⁷⁷Lu-PSMA infusions. Any-grade treatment-emergent AEs were reported in 79% (105/133) of patients and serious AEs in 30% (40/133). The most frequent grade 3-4 laboratory abnormalities were anemia (30%, 40/133) and thrombocytopenia (13%, 17/133). Median overall survival was 13.2 mo (95% CI, 10.5-15.6 mo) from the start of ¹⁷⁷Lu-PSMA. Conclusion: In this real-world setting, ²²³Ra followed by ¹⁷⁷Lu-PSMA therapy in heavily pretreated patients with mCRPC was clinically feasible, with no indication of impairment of ¹⁷⁷Lu-PSMA safety or effectiveness.