Imaging of CTLA4 Blockade-Induced Cell Replication with 18F-FLT PET in Patients with Advanced Melanoma Treated with Tremelimumab

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. Methods: 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 F-18-FDG and cell replication with the PET probe 3'-deoxy-3'-F-18-fluorothymidine (F-18-FLT). Results: PET/CT scans obtained at a median of 2 mo after initial dosing did not demonstrate significant changes in lesion size or F-18-FDG or F-18-FLT uptake when focusing on metastatic lesions. Similarly, there was no difference in F-18-FDG uptake in the non-melanoma-involved spleen. However, there were significant increases in standardized uptake values for F-18-FLT in the spleen using post-and pretremelimumab treatment scans. Conclusion: Molecular imaging with the PET probe F-18-FLT allows mapping and noninvasive imaging of cell proliferation in secondary lymphoid organs after CTLA4 blockade in patients with metastatic melanoma.