Early Detection of Checkpoint Inhibitor-Associated Myocarditis Using 68Ga-FAPI PET/CT

Daniel Finke; Markus B Heckmann; Esther Herpel; Hugo A Katus; Uwe Haberkorn; Florian Leuschner; Lorenz H Lehmann

doi:10.3389/fcvm.2021.614997

Early Detection of Checkpoint Inhibitor-Associated Myocarditis Using ⁶⁸Ga-FAPI PET/CT

Front Cardiovasc Med. 2021 Feb 25:8:614997. doi: 10.3389/fcvm.2021.614997. eCollection 2021.

Authors

Daniel Finke^{1

2}, Markus B Heckmann^{1

2}, Esther Herpel³, Hugo A Katus^{1

2}, Uwe Haberkorn^{4

5

6}, Florian Leuschner^{1

2}, Lorenz H Lehmann^{1

2

7}

Affiliations

¹ Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany.
² DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
³ Department of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
⁴ Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
⁵ Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶ Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
⁷ German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abstract

Objective: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-associated myocarditis. Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n = 23) to three patients with suspected ICI-associated myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. All three patients' myocardial biopsies were examined for inflammatory cells. Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1,771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients' FAPI PET/CTs showed cardiac enrichment of the marker which was less distinct or absent in patients receiving ICIs without any signs of immunological adverse effects or cardiac impairment (n = 23) [Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)]. Conclusions: Apart from the successful implementation of ICIs in oncological treatments, ICI-associated myocarditis is still a challenging adverse effect. FAPI PET/CT may be used in order to identify affected patients at an early stage. Moreover, when integrated into cancer stage diagnostics, it contributes to cardiac risk stratification besides biomarker, ECG and echocardiography.

Keywords: cardio-oncology; cardiotoxcity; checkpoint- inhibitors; myocarditis; positron emission tomography.