Diagnosis of myocarditis is challenging because of non-specific clinical presentation of the disease. 18F-FDG PET/CT detects cardiac inflammation. However, non-specific physiological myocardial 18F-FDG uptake impairs the diagnostic accuracy. Current imaging techniques lack specificity for detecting active myocardial inflammation. This study evaluates the efficacy of three Positron Emission Tomography (PET) tracers for identifying myocardial inflammation in experimental autoimmune myocarditis (EAM) rat model and their potential applications in human cardiac sarcoidosis (CS).

Myocarditis was induced by immunizing rats with porcine cardiac myosin in complete Freund’s adjuvant. Control rats were injected with Freund’s adjuvant alone. Three PET tracers were used in three studies followed by in vivo PET/computed tomography (CT) imaging and ex vivo autoradiography to study tracers’ uptake. Tissue sections of EAM rats and myocardial autopsy samples of patients with CS were studied for folate receptor β (FR-β) and vascular adhesion protein-1 (VAP-1) expression. The first tracer, 18F-FOL, targets FR-β on activated macrophages. The second tracer, [68Ga]Ga-NODAGA-RGD, targets αvβ3 integrin, which is upregulated during angiogenesis and inflammation. The third tracer, [68Ga]Ga-DOTA-Siglec-9, targets VAP-1 associated with leukocyte trafficking. PET/CT imaging with these tracers showed increased uptake in inflamed myocardium compared to non-inflamed myocardium and healthy controls. This uptake was confirmed by ex vivo autoradiography. FR-β and VAP- 1 were expressed in human cardiac sarcoid lesions.

In conclusion, 18F-FOL, [68Ga]Ga-NODAGA-RGD, and [68Ga]Ga-DOTA-Siglec-9 PET tracers show potential for detecting myocardial inflammation, with potential applicability in human cardiac sarcoidosis.