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Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes
J L Goggi1, Y X Tan1, S V Hartimath1
1Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A* STAR), 11 Biopolis Way, #01-02, Helios, 138667, Singapore.
Molecular Imaging and Biology
|July 25, 2020
Summary
This study shows that [18F]AlF-mNOTA-GZP PET imaging can predict immune checkpoint inhibitor (ICI) response by tracking CD8+ T cells. However, tumor characteristics can affect imaging accuracy, requiring careful interpretation for safe cancer therapy management.
Area of Science:
- Oncology
- Immunology
- Radiochemistry
Background:
- Immune checkpoint inhibitors (ICIs) are crucial for cancer treatment, but their efficacy varies. Combination therapies show promise but increase risks of adverse events.
- Non-invasive stratification of ICI response is needed for safe and effective cancer therapy management across diverse phenotypes.
Purpose of the Study:
- To evaluate the utility of a novel PET imaging tracer, [18F]AlF-mNOTA-GZP, targeting granzyme B, for stratifying ICI response in preclinical colon cancer models.
- To correlate in vivo tracer uptake with changes in tumor-associated immune cell populations.
Main Methods:
- Two syngeneic colon cancer models (CT26 and MC38) were used to assess [18F]AlF-mNOTA-GZP uptake.
- Tumor uptake was measured after ICI monotherapy and combination therapy (with PD-1).
- Uptake was correlated with immune cell populations, particularly T cells.
Main Results:
- [18F]AlF-mNOTA-GZP demonstrated good predictive ability, correlating with CD8+ T cell changes.
- Significant differences in tracer uptake and response were observed between CT26 and MC38 models, attributed to distinct tumor microenvironments (MSI-high in MC38).
Conclusions:
- [18F]AlF-mNOTA-GZP PET imaging can stratify tumor response to ICIs by reflecting CD8+ T cell dynamics.
- Preexisting tumor phenotypic abnormalities can influence tracer uptake, potentially complicating data interpretation and necessitating cautious application in clinical settings.
