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.

State-of-the-art of FAPI-PET imaging: a systematic review and meta-analysis

“…Switching the radioisotope, following in the footsteps of prostate-speci c membrane antigen radiopharmaceuticals, could grant a better resolution, other than facilitating the commercial distribution of this tracer. [25]; it could serve as a biomarker, working in synergy with the well-established cardiovascular prognostic risk factors [29], and it might have a role to assess treatment-related cardiotoxicity [35]. In rheumatological studies, [ 68 Ga]Ga-FAPI proved to complement [ 18 F]FDG information targeting brosis and in ammation, respectively [24,26].…”

“…One study was designed as a phase I investigation [24]. In 12/23 studies [ 68 Ga]Ga-FAPI was offered as a compassionate drug according to the German Medicinal Product Act § 13(2b) [25,26,35,36,[27][28][29][30][31][32][33][34]. In the remaining 10/23 papers, the trial phase was not speci ed or designated as "not applicable" [37][38][39][40][41][42][43][44][45][46].…”

“…Data were con rmed in a validation cohort of 44 patients. Finke et al[35] found a higher myocardial [ 68 Ga]Ga-FAPI uptake in patients with suspected checkpoint inhibitor-associated myocarditis (n = 3) than in those without any signs of cardiac disease (n = 23).3.2.1.2Non-oncological studies focused on rheumatological diseases. On a per-patient analysis, [ 68 Ga]Ga-FAPI PET/CT was positive in all subjects, while [ 18 F]FDG missed two cases.…”

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images

“…For example, radiation may induce fibrosis, limiting the usefulness of FAPI PET for decision making after therapy. Moreover, fibroblast activation could be associated with chronic inflammation, liver and lung fibrosis, and checkpoint inhibitor-associated myocarditis, reducing the specificity and limit the diagnostic value of FAPI PET, so further studies are needed [207][208][209].…”

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to in-Vivo Images

“…For example, radiation may induce fibrosis, limiting the usefulness of FAPI PET for decision making after therapy. Moreover, fibroblast activation could be associated with chronic inflammation, with liver and lung fibrosis and with checkpoint inhibitor-associated myocarditis, reducing the specificity and limit the diagnostic value of FAPI PET and further studies are needed [197][198][199].…”