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J Nucl Med. 2010 Mar;51(3):340-6. doi: 10.2967/jnumed.109.070946. Epub 2010 Feb 11.

Imaging of CTLA4 blockade-induced cell replication with (18)F-FLT PET in patients with advanced melanoma treated with tremelimumab.

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Division of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA.


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.

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