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First published online February 11, 2010, 10.2967/jnumed.109.070946
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Journal of Nuclear Medicine Vol. 51 No. 3 340-346
© 2010 by Society of Nuclear Medicine
doi: 10.2967/jnumed.109.070946

Clinical Investigation

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

Antoni Ribas1–3, Matthias R. Benz4, Martin S. Allen-Auerbach4, Caius Radu2–4, Bartosz Chmielowski1, Elizabeth Seja1, John L. Williams4, Jesus Gomez-Navarro5, Timothy McCarthy5 and Johannes Czernin2–4

1 Division of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California; 2 Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California; 3 Institute of Molecular Medicine, UCLA, Los Angeles, California; 4 Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California; and 5 Pfizer Global Research and Development, New London, Connecticut

Correspondence: For correspondence or reprints contact: Antoni Ribas, Division of Hematology/Oncology, 11-934 Factor Bldg., UCLA Medical Center, 10833 Le Conte Ave., Los Angeles, CA 90095-1782. E-mail: aribas{at}mednet.ucla.edu

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.

Key Words: monoclonal antibodies • oncology • PET • FLT • lymphocyte proliferation • tumor immunology

Guest Editor: Steve Larson, Memorial Sloan-Kettering Cancer Center

COPYRIGHT © 2010 by the Society of Nuclear Medicine, Inc.


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