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

Abstract

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