Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes
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RESEARCH ARTICLE
Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes J. L. Goggi,1 Y. X. Tan,1 S. V. Hartimath,1 B. Jieu,2 Y. Y. Hwang,3 L. Jiang,1 R. Boominathan,1 P. Cheng,1 T. Y. Yuen,2 H. X. Chin,3 J. R. Tang,1 A. Larbi,3 A. M. Chacko,4 L. Renia,3 C. Johannes,5 Edward G. Robins 1,6 1
Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A* STAR), 11 Biopolis Way, #01-02, Helios, 138667, Singapore 2 Institute of Chemical and Engineering Sciences (ICES), A*STAR, 8 Biomedical Grove, #07, Neuros, 138665, Singapore 3 Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Immunos, 138648, Singapore 4 Laboratory for Translational and Molecular Imaging (LTMI), Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore 5 p53 Laboratory, A*STAR, 8A Biomedical Grove, #06-04/05, Neuros/Immunos, 138665, Singapore 6 Clinical Imaging Research Centre (CIRC), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore
Abstract Purpose: Immune checkpoint inhibitor (ICI) monotherapy and combination regimens are being actively pursued as strategies to improve durable response rates in cancer patients. However, the biology surrounding combination therapies is not well understood and may increase the likelihood of immune-mediated adverse events. Accurate stratification of ICI response by non-invasive PET imaging may help ensure safe therapy management across a wide number of cancer phenotypes. Procedures: We have assessed the ability of a fluorine-labelled peptide, [18F]AlF-mNOTA-GZP, targeting granzyme B, to stratify ICI response in two syngeneic models of colon cancer, CT26 and MC38. In vivo tumour uptake of [18F]AlF-mNOTA-GZP following ICI monotherapy, or in combination with PD-1 was characterised and correlated with changes in tumour-associated immune cell populations. Results: [18F]AlF-mNOTA-GZP showed good predictive ability and correlated well with changes in tumour-associated T cells, especially CD8+ T cells; however, overall uptake and response to monotherapy or combination therapies was very different in the CT26 and MC38 tumours, likely due to the immunostimulatory environment imbued by the MSI-high phenotype in MC38 tumours. Conclusions: [18F]AlF-mNOTA-GZP uptake correlates well with changes in CD8+ T cell populations and is able to stratify tumour response to a range of ICIs administered as monotherapies or in combination. However, tracer uptake can be significantly affected by preexisting phenotypic abnormalities potentially confusing data interpretation. Key words: Immune checkpoint inhibitor (ICI), [18F]AlF-mNOTA-GZP, CT26, MC38
Electronic supplementary material The online version of this article (https:// doi.org/10.1007/s11307-020-01519-3) contains supplementary material, which is available to authorized users. Correspondence to: Edward Robins; e-mail: [email protected]
Goggi J.L. et al.: Imaging Immunotherapy Combinations
Introduction Immu
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