Imaging of CTLA4 blockade-induced cell replication with (18)F-FLT PET in patients with advanced melanoma treated with tremelimumab.
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 (18)F-FDG and cell replication with the PET probe 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT).


RESULTS
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.


CONCLUSIONS
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.
Division of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, California, USA. aribas@mednet.ucla.edu
Antoni
A
Ribas
Matthias R
MR
Benz
Martin S
MS
Allen-Auerbach
Caius
C
Radu
Bartosz
B
Chmielowski
Elizabeth
E
Seja
John L
JL
Williams
Jesus
J
Gomez-Navarro
Timothy
T
McCarthy
Johannes
J
Czernin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000378:metabolism*; D060908:CTLA-4 Antigen; D049109:Cell Proliferation / Q000187:drug effects; D015224:Dideoxynucleosides; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D013154:Spleen / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D015224:Dideoxynucleosides; D019788:Fluorodeoxyglucose F18; C002854:alovudine; C520704:tremelimumab