Division of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.
J Nucl Med. 2010 Mar;51(3):340-6. doi: 10.2967/jnumed.109.070946. Epub 2010 Feb 11.
Preclinical models predict that blockade of the coinhibitory molecule cytotoxic T lymphocyte-associated antigen 4 (CTLA4) on lymphocytes results in the release of a cell cycle inhibitory checkpoint, allowing lymphocyte proliferation, tumor targeting, and regression. However, there is a paucity of data demonstrating that lymphocyte proliferation does occur in humans treated with CTLA4-blocking antibodies.
We tested the role of whole-body molecular imaging in patients with advanced melanoma receiving the CTLA4-blocking antibody tremelimumab, allowing the analysis of changes in glucose metabolism using the PET probe (18)F-FDG and cell replication with the PET probe 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT).
PET/CT scans obtained at a median of 2 mo after initial dosing did not demonstrate significant changes in lesion size or (18)F-FDG or (18)F-FLT uptake when focusing on metastatic lesions. Similarly, there was no difference in (18)F-FDG uptake in the non-melanoma-involved spleen. However, there were significant increases in standardized uptake values for (18)F-FLT in the spleen using post- and pretremelimumab treatment scans.
Molecular imaging with the PET probe (18)F-FLT allows mapping and noninvasive imaging of cell proliferation in secondary lymphoid organs after CTLA4 blockade in patients with metastatic melanoma.
临床前模型预测，淋巴细胞上细胞毒性 T 淋巴细胞相关抗原 4（CTLA4）的抑制性分子阻断会导致细胞周期抑制检查点释放，从而允许淋巴细胞增殖、肿瘤靶向和消退。然而，缺乏数据表明接受 CTLA4 阻断抗体治疗的人类中确实发生了淋巴细胞增殖。
我们测试了全身分子成像在接受 CTLA4 阻断抗体 tremelimumab 治疗的晚期黑色素瘤患者中的作用，允许使用 PET 探针（18）F-FDG 分析葡萄糖代谢的变化，并用 PET 探针 3'-脱氧-3'-(18)F-氟胸苷 ((18)F-FLT) 分析细胞复制。
在初始给药后中位数为 2 个月获得的 PET/CT 扫描显示，当聚焦于转移性病变时，病变大小或（18）F-FDG 或（18）F-FLT 摄取均无明显变化。同样，非黑色素瘤受累脾脏中（18）F-FDG 摄取也没有差异。然而，使用 tremelimumab 治疗前后扫描，脾脏中（18）F-FLT 的标准化摄取值有显著增加。
使用 PET 探针（18）F-FLT 的分子成像允许在转移性黑色素瘤患者中 CTLA4 阻断后对次级淋巴器官中的细胞增殖进行定位和无创成像。
