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Open Access 01-10-2020 | Checkpoint Inhibitors | Research Article

Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes

Authors: J. L. Goggi, Y. X. Tan, S. V. Hartimath, B. Jieu, Y. Y. Hwang, L. Jiang, R. Boominathan, P. Cheng, T. Y. Yuen, H. X. Chin, J. R. Tang, A. Larbi, A. M. Chacko, L. Renia, C. Johannes, Edward G. Robins

Published in: Molecular Imaging and Biology | Issue 5/2020

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.

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Title: Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes
Authors: J. L. Goggi
Y. X. Tan
S. V. Hartimath
B. Jieu
Y. Y. Hwang
L. Jiang
R. Boominathan
P. Cheng
T. Y. Yuen
H. X. Chin
J. R. Tang
A. Larbi
A. M. Chacko
L. Renia
C. Johannes
Edward G. Robins
Publication date: 01-10-2020
Publisher: Springer International Publishing
Keywords: Checkpoint Inhibitors
Colon Cancer
Colon Cancer
Published in: Molecular Imaging and Biology / Issue 5/2020
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-020-01519-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes

Abstract

Purpose

Procedures

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

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