PT  - JOURNAL ARTICLE
AU  - Antoni Ribas
AU  - Matthias R. Benz
AU  - Martin S. Allen-Auerbach
AU  - Caius Radu
AU  - Bartosz Chmielowski
AU  - Elizabeth Seja
AU  - John L. Williams
AU  - Jesus Gomez-Navarro
AU  - Timothy McCarthy
AU  - Johannes Czernin
TI  - Imaging of CTLA4 Blockade–Induced Cell Replication with <sup>18</sup>F-FLT PET in Patients with Advanced Melanoma Treated with Tremelimumab
AID  - 10.2967/jnumed.109.070946
DP  - 2010 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 340--346
VI  - 51
IP  - 3
4099  - http://jnm.snmjournals.org/content/51/3/340.short
4100  - http://jnm.snmjournals.org/content/51/3/340.full
SO  - J Nucl Med2010 Mar 01; 51
AB  - 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.