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Ferreira CA, Heidari P, Ataeinia B, et al. Non-invasive Detection of Immunotherapy-Induced Adverse Events. Clin Cancer Res. 2021;doi: 10.1158/1078-0432.CCR-20-4641.
Ferreira, C. A., Heidari, P., Ataeinia, B., Sinevici, N., Sise, M. E., Colvin, R. B., Wehrenberg-Klee, E., & Mahmood, U. (2021). Non-invasive Detection of Immunotherapy-Induced Adverse Events. Clinical cancer research : an official journal of the American Association for Cancer Research, . https://doi.org/10.1158/1078-0432.CCR-20-4641
Ferreira, Carolina A, et al. "Non-invasive Detection of Immunotherapy-Induced Adverse Events." Clinical cancer research : an official journal of the American Association for Cancer Research vol. (2021). doi: https://doi.org/10.1158/1078-0432.CCR-20-4641
Ferreira CA, Heidari P, Ataeinia B, Sinevici N, Sise ME, Colvin RB, Wehrenberg-Klee E, Mahmood U. Non-invasive Detection of Immunotherapy-Induced Adverse Events. Clin Cancer Res. 2021 Jul 12; doi: 10.1158/1078-0432.CCR-20-4641. Epub 2021 Jul 12. PMID: 34253581; PMCID: PMC8752648.
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Clin Cancer Res. 2021 Jul 12; doi: 10.1158/1078-0432.CCR-20-4641. Epub 2021 Jul 12.

Non-invasive Detection of Immunotherapy-Induced Adverse Events.

Clinical cancer research : an official journal of the American Association for Cancer Research

Carolina A Ferreira, Pedram Heidari, Bahar Ataeinia, Nicoleta Sinevici, Meghan E Sise, Robert B Colvin, Eric Wehrenberg-Klee, Umar Mahmood

Affiliations

  1. Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
  2. Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
  3. Department of Pathology and Medicine, Massachusetts General Hospital, Boston, Massachusetts.
  4. Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts. [email protected].

PMID: 34253581 PMCID: PMC8752648 DOI: 10.1158/1078-0432.CCR-20-4641

Abstract

PURPOSE: Cancer immunotherapy has markedly improved the prognosis of patients with a broad variety of malignancies. However, benefits are weighed against unique toxicities, with immune-related adverse events (irAE) that are frequent and potentially life-threatening. The diagnosis and management of these events are challenging due to heterogeneity of timing onset, multiplicity of affected organs, and lack of non-invasive monitoring techniques. We demonstrate the use of a granzyme B-targeted PET imaging agent (GZP) for irAE identification in a murine model.

EXPERIMENTAL DESIGN: We generated a model of immunotherapy-induced adverse events in Foxp3-DTR-GFP mice bearing MC38 tumors. GZP PET imaging was performed to evaluate organs non-invasively. We validated imaging with

RESULTS: GZP PET imaging revealed differential uptake in organs affected by irAEs, such as colon, spleen, and kidney, which significantly diminished after administration of the immunosuppressor dexamethasone. The presence of granzyme B and immune infiltrates were confirmed histologically and correlated with significantly higher uptake in PET imaging. The presence of granzyme B was also confirmed in samples from patients that presented with clinical irAEs.

CONCLUSIONS: We demonstrate an interconnection between the establishment of irAEs and granzyme B presence and, for the first time, the visualization of those events through PET imaging.

©2021 American Association for Cancer Research.

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