64Cu-GRIP B in Patients With Acute Myocarditis

Summary

The proposed patient study represents the first-ever acute myocarditis patient imaging study with 64Cu-GRIP B PET. The tracer is designed to detect extracellular granzyme B as it is secreted by activated cytotoxic T lymphocytes in the cardiomyocyte inflammatory microenvironment, highlighting areas of CD8 T cell activity leading to cardiomyocyte damage. Myocarditis is characterized pathologically by myocardial infiltration of T cells and macrophages with presence of cardiomyocyte death - the proposed tracer tests for both the accumulation of CD8 T cells and their cytotoxic activity, which will hopefully significantly improve diagnostic certainty. The study population is focused on patients with acute myocarditis to assess the specificity and sensitivity of 64Cu-GRIP B to detect myocarditis. In future studies, 64Cu-GRIP B PET may also serve as a biomarker to monitor early response to immunomodulatory therapies to treat acute myocarditis. Each year at UCSF, the investigators encounter about 20 patients with acute myocarditis. These patients often present with non-specific cardiac symptoms with some evidence of cardiac injury (abnormal electrocardiogram or elevation in cardiac biomarkers such as troponin). Rarely is the diagnosis clear and often numerous additional clinical studies are necessary to rule out other common causes of cardiac injury like myocardial infarction. Patients identified with acute myocarditis by the investigators will receive standard clinical testing as appropriate and will also be consented to participate in a PET study with 64Cu-GRIP B. Over the course of this proposal, the investigators expect to enroll 10 patients who are being evaluated for acute myocarditis determined by current standard of care diagnostic modalities. The investigators will perform this feasibility assessment in parallel to the usual clinical care.

Timeline

Start

2026-08

Primary completion

2030-11

Completion

2031-01

Publications

• Background Fankhauser RG, Johnson DB, Moslehi JJ, Balko JM. Preclinical mouse models of immune checkpoint inhibitor-associated myocarditis. Nat Cardiovasc Res. 2025 May;4(5):526-538. doi: 10.1038/s44161-025-00640-2. Epub 2025 May 7.
• Background Song EJ, Joachimbauer A, Tasca S, Baylis R, Schmidt D, Ludewig B, Moslehi JJ. T cells in acute and chronic myocarditis: from diagnosis to treatment. Eur Heart J. 2026 May 18;47(19):2255-2270. doi: 10.1093/eurheartj/ehaf1080.
• Background Ehlerding EB, England CG, McNeel DG, Cai W. Molecular Imaging of Immunotherapy Targets in Cancer. J Nucl Med. 2016 Oct;57(10):1487-1492. doi: 10.2967/jnumed.116.177493. Epub 2016 Jul 28.
• Background Zhao N, Bardine C, Lourenco AL, Wang YH, Huang Y, Cleary SJ, Wilson DM, Oh DY, Fong L, Looney MR, Evans MJ, Craik CS. In Vivo Measurement of Granzyme Proteolysis from Activated Immune Cells with PET. ACS Cent Sci. 2021 Oct 27;7(10):1638-1649. doi: 10.1021/acscentsci.1c00529. Epub 2021 Sep 2.
• Background Zhang L, Zlotoff DA, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F, Zubiri L, Chen CL, Sullivan RJ, Alvi RM, Rokicki A, Murphy SP, Jones-O'Connor M, Heinzerling LM, Barac A, Forrestal BJ, Yang EH, Gupta D, Kirchberger MC, Shah SP, Rizvi MA, Sahni G, Mandawat A, Mahmoudi M, Ganatra S, Ederhy S, Zatarain-Nicolas E, Groarke JD, Tocchetti CG, Lyon AR, Thavendiranathan P, Cohen JV, Reynolds KL, Fradley MG, Neilan TG. Major Adverse Cardiovascular Events and the Timing and Dose of Corticosteroids in Immune Checkpoint Inhibitor-Associated Myocarditis. Circulation. 2020 Jun 16;141(24):2031-2034. doi: 10.1161/CIRCULATIONAHA.119.044703. Epub 2020 Jun 15. No abstract available.
• Background Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol. 2018 Dec 18;72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072.
• Background Ammirati E, Moslehi JJ. Diagnosis and Treatment of Acute Myocarditis: A Review. JAMA. 2023 Apr 4;329(13):1098-1113. doi: 10.1001/jama.2023.3371.

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