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.
Highlights
These observations, a detailed cardiological assessment, including catherization with myocardial biopsy, echocardiography and cardiac MRI, is initiated
Reconstruction was conducted with an ordered subset expectation maximization (OSEM) algorithm with two iterations/21 subsets and Gauss-filtered to a transaxial resolution of 5 mm at full-width half-maximum (FWHM)
Three patients receiving immune checkpoint inhibitors were admitted with suspected autoimmune myocarditis (Table 1)
Summary
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. From 2017 to 2019, 26 patients were treated with PD-1, PD-L1, or CTLA-4 inhibitors at University Hospital Heidelberg because of their malignant disease and received 68Ga-FAPI PET/CT scans to asses their cancer stage. FAPI PET/CT scans were performed using 122–336 mBq of Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) which was administered intravenously 60 min before examination. Attenuation correction was performed using the low-dose non-enhanced CT data. The quantitative assessment of standardized uptake values (SUV) was done using a region of interest technique
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