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

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.

Figure 1

FAPI PET/CT illustrates ICI-associated myocarditis. (A) Bulls Eye Illustration of standardized uptake values (SUVs) showing their distribution in the myocardium of the left ventricle in 17 defined areas. The enrichment is shown for ICI-associated myocarditis patients #1–#3. (B) In comparison, the median signal of patients which have received immune checkpoint inhibitors (n = 23) without signs of myocarditis is summarized. (C) Exemplary images of ⁶⁸Ga-FAPI PET/CT showing tracer uptake in the myocarditis patients' left ventricle and one example for the diagnostic findings in a non-myocarditis patient (right). (D) Exemplary histological sections of the left ventricle (HE: Hematoxylin staining, CD3- and CD8-immunostaining), confirming autoimmune myocarditis.

Figure 2

Initial presentation of ICI-associated myocarditis patients. Initial ECG at presentation in the hospital when ICI-associated myocarditis was diagnosed. Patient #1: 25 mm/s, patient #2: 25 mm/s, patient #2, patient #3: 50 mm/s.