RT Journal Article
SR Electronic
T1 Quantitative CD3 PET Imaging Predicts Tumor Growth Response to Anti-CTLA-4 Therapy
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1607
OP 1611
DO 10.2967/jnumed.116.173930
VO 57
IS 10
A1 Benjamin M. Larimer
A1 Eric Wehrenberg-Klee
A1 Alexander Caraballo
A1 Umar Mahmood
YR 2016
UL http://jnm.snmjournals.org/content/57/10/1607.abstract
AB Immune checkpoint inhibitors have made rapid advances, resulting in multiple Food and Drug Administration–approved therapeutics that have markedly improved survival. However, these benefits are limited to a minority subpopulation that achieves a response. Predicting which patients are most likely to benefit would be valuable for individual therapy optimization. T-cell markers such as CD3—by examining active recruitment of the T cells responsible for cancer-cell death—represent a more direct approach to monitoring tumor immune response than pretreatment biopsy or genetic screening. This approach could be especially effective as numerous different therapeutic strategies emerge, decreasing the need for drug-specific biomarkers and instead focusing on T-cell infiltration, which has been previously correlated with treatment response. Methods: A CD3 PET imaging agent targeting T cells was synthesized to test the role of such imaging as a predictive marker. The 89Zr-p-isothiocyanatobenzyl-deferoxamine-CD3 PET probe was assessed in a murine tumor xenograft model of anti–cytotoxic T-lymphocyte antigen-4 (CTLA-4) immunotherapy of colon cancer. Results: Imaging on day 14 revealed 2 distinct groups of mice stratified by PET signal intensity. Although there was no significant difference in tumor volume on the day of imaging, in the high-uptake group subsequent measurements revealed significantly smaller tumors than in either the low-uptake group or the untreated controls. In contrast, there was no significant difference in the size of tumors between the low-uptake and untreated control mice. Conclusion: These findings indicate that high CD3 PET uptake in the anti-CTLA-4–treated mice correlated with subsequent reduced tumor volume and was a predictive biomarker of response.