PET/CT Myocardial Inflammation Imaging in Myocarditis Rats by Using a Translocator Protein Tracer 18F-FDPA

Introduction: In this study, a translocator protein 18 kDa (TSPO) targeted radiotracer, N,N-diethyl-2-(2-(4-¹⁸F-fluorophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide (¹⁸F-FDPA) was evaluated as a potential non-invasive imaging agent of myocarditis.

Methods: ¹⁸F-FDPA was radiolabeled automatically by a one-step nucleophilic reaction. Rats in myocarditis group were injected 0.2 mL porcine myosin suspension (1 mg myosin in 0.1 mL buffered aqueous glycerol solution mixed with 0.1 mL Freund's complete adjuvant) into the foot pad at Day 1 and Day 7. On Day 21, normal rats (n=4) and myocarditis rats (n=4) were injected about 30 MBq ¹⁸F-FDPA, and PET/CT imaging was underwent (Inveon PET/CT, Siemens, Germany) at 30 min post injection. Global heart uptake of ¹⁸F-FDPA in normal and myocarditis rats were analyzed by Inveon Research Workplace. Maximum standardized uptake value (SUV_max) and mean standardized uptake value (SUV_mean) were quantitatively obtanined After PET/CT imaging, the hearts were harvested. The hematoxylin and eosin (HE) staining, TSPO and CD68 immunofluorescence staining were performed. The inflammation and normal myocardium region in myocarditis rats were defined by HE staining, respectively. The target to background ratio (TBR) in each rat between inflammation region and normal region was calculated as: TBR = SUV_mean in the inflammation region / SUV_mean in the normal region.

Results: The total synthesis time of ¹⁸F-FDPA was 68 min using CFN-MPS200 module. The non-decay corrected radiochemical yields were 19.8 ± 2.8% (n = 6). The radiochemical purities were ≥ 99%. The molar activities were 140-225 GBq/μmol. The SUV_mean (5.12 ± 0.38 vs. 3.18 ±0.09, P<0.001) and SUV_max (8.80 ± 0.82 vs. 6.35 ± 1.08, P=0.011) in myocarditis rats were significantly high than that in normal rats. The HE staining result indicated that the hearts in myocarditis rats were infiltrated with massive inflammatory cells and the TBR of ¹⁸F-FDPA in the inflammation region was 1.64 ± 0.16. The immunofluorescence staining in these regions showed positive TSPO expression, as well as positive CD68 expression, indicating the increased myocardium uptake of ¹⁸F-FDPA was related with macrophages.

Conclusions: High ¹⁸F-FDPA activity was revealed in the myocarditis rats, especially in the myocardial regions infiltrated with macrophages. ¹⁸F-FDPA could be a potential cardiac inflammation imaging agent.

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