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

Journal of Nuclear Medicine

Antoni Ribas¹  Johannes Czernin¹  Elizabeth Seja¹  Timothy McCarthy¹  Caius Radu¹  Jesus Gomez-Navarro¹  Bartosz Chmielowski¹  John L. Williams¹  Matthias R. Benz¹  Martin S. Allen-Auerbach¹ 

关键词: monoclonal antibodies;    oncology;    PET;    FLT;    lymphocyte proliferation;    tumor immunology;   

DOI  :  10.2967/jnumed.109.070946

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown