Lynch Shannon E, Crawford Corinne, Hunt Addison L, Sligh Luke L, Zhang Yujun, Norian Lyse A, Larimer Benjamin M, Lapi Suzanne E, Sorace Anna G
Graduate Biomedical Sciences, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama.
J Nucl Med. 2025 Jul 1;66(7):1039-1045. doi: 10.2967/jnumed.124.268938.
The effects of obesity on cancer treatment efficacy remain unclear, as both beneficial and detrimental modulations of the tumor immune microenvironment have been reported. We compared Ga-NOTA-GZP (βAla-Gly-Gly-Ile-Glu-Phe-Asp-CHO) PET images with those obtained with the gold standard, F-FDG PET, to quantify biologic variations in a diet-induced obesity model of triple-negative breast cancer to understand how obesity influences the tumor immune landscape and response to immunotherapy. C57BL6/J mice were fed a high-fat diet ( = 24) or low-fat diet ( = 18) for 14 wk. EO771 tumor-bearing mice were treated with a fixed or weight-based dose of saline or checkpoint-blockade immunotherapy, and tumor volume was evaluated for long-term response. Mice were imaged via Ga-NOTA-GZP PET on day 7 to quantify immune activation, and those images were compared with F-FDG PET images to characterize changes in glucose metabolism on days 0 and 6. SUV was quantified from imaging data, and a cohort of mice was euthanized to validate biologic changes via flow cytometry. Mice fed a high-fat diet demonstrated increased tumor glucose metabolism at baseline, as measured by F-FDG PET. No significant differences were observed in F-FDG SUV for responder tumors on day 6. The Ga-NOTA-GZP PET signal was increased in tumors responsive to immunotherapy on day 7 and was highly sensitive in predicting response via analysis of receiver-operating-characteristic curves. Obesity decreases response to immunotherapy by altering metabolism and the tumor immune microenvironment. Ga-NOTA-GZP PET imaging is a sensitive and predictive imaging biomarker of immunotherapy response, but weight-based dosing is needed to achieve effective changes in tumor volume.
肥胖对癌症治疗疗效的影响仍不明确，因为有报道称肿瘤免疫微环境存在有益和有害的调节作用。我们将Ga-NOTA-GZP（β-丙氨酸-甘氨酸-甘氨酸-异亮氨酸-谷氨酸-苯丙氨酸-天冬氨酸-醛）PET图像与金标准F-FDG PET图像进行比较，以量化三阴性乳腺癌饮食诱导肥胖模型中的生物学差异，从而了解肥胖如何影响肿瘤免疫格局和对免疫治疗的反应。C57BL6/J小鼠被喂食高脂饮食（n = 24）或低脂饮食（n = 18）14周。对携带EO771肿瘤的小鼠给予固定剂量或基于体重的生理盐水或检查点阻断免疫治疗，并评估肿瘤体积以观察长期反应。在第7天通过Ga-NOTA-GZP PET对小鼠进行成像以量化免疫激活，并将这些图像与F-FDG PET图像进行比较，以表征第0天和第6天葡萄糖代谢的变化。从成像数据中量化SUV，并对一组小鼠实施安乐死以通过流式细胞术验证生物学变化。通过F-FDG PET测量，喂食高脂饮食的小鼠在基线时肿瘤葡萄糖代谢增加。在第6天，反应性肿瘤的F-FDG SUV未观察到显著差异。在第7天，对免疫治疗有反应的肿瘤中Ga-NOTA-GZP PET信号增加，并且通过分析受试者工作特征曲线，其在预测反应方面具有高度敏感性。肥胖通过改变代谢和肿瘤免疫微环境降低对免疫治疗的反应。Ga-NOTA-GZP PET成像为免疫治疗反应的一种敏感且具有预测性的成像生物标志物，但需要基于体重的给药方式才能实现肿瘤体积的有效变化。
