Early detection of radiation-induced myocardial damage by [¹⁸F]AlF-NOTA-FAPI-04 PET/CT imaging

Purpose: Retrospective analysis revealed increased [¹⁸F]AlF-NOTA-FAPI-04 uptake in the myocardium of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). This study investigated and verified the feasibility of [¹⁸F]AlF-NOTA-FAPI-04 PET/CT for detecting radiation-induced myocardial damage (RIMD).

Methods: Myocardial FAPI uptake was analyzed before and during radiotherapy in thirteen ESCC patients treated with CCRT. In the animal study, a single dose of 50 Gy was delivered to the cardiac apex of Wistar rats (24 rats, including 16 RIMD model rats and 8 control model rats). RIMD model rats were scanned with [¹⁸F]AlF-NOTA-FAPI-04 PET/CT weekly for 12 weeks, and left ventricular ejection fraction (LVEF) was measured by magnetic resonance imaging. Dynamic, blocking, and [¹⁸F]FDG PET/CT studies (4 rats/group) were performed on RIMD rats at 5 weeks post-radiation, and histopathological analyses were conducted.

Results: Increased FAPI uptake in the myocardium was found after CCRT (1.53 ± 0.53 vs 1.88 ± 0.70, P = 0.015). In RIMD rats, significantly increased FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure and peaked in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardium than in the remote myocardium, as identified by decreased [¹⁸F]FDG uptake and confirmed by autoradiography, hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. The LVEF remained unchanged at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week.

Conclusion: Through clinical phenomena and animal experimental studies, this study indicated that [¹⁸F]AlF-NOTA-FAPI-04 PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF, indicating the clinical potential of [¹⁸F]AlF-NOTA-FAPI-04 as a PET/CT tracer for early monitoring of RIMD.