[¹⁸F]MFBG PET/CT imaging of myocardial sympathetic innervation in healthy controls and patients with parkinson's disease: dosimetry and pharmacokinetics.

Abstract

Cardiac noradrenergic denervation visualized by meta-[¹²³I]iodobenzylguanidine ([¹²³I]MIBG) imaging supports the diagnosis of Parkinson's disease (PD). Recently, meta-[¹⁸F] fluorobenzylguanidine ([¹⁸F]MFBG) PET demonstrated favorable imaging characteristics compared with [¹²³I]MIBG scintigraphy for neuroendocrine tumors. We assessed [¹⁸F]MFBG dosimetry and myocardial pharmacokinetics in healthy controls and PD patients. For dosimetry, three controls underwent sequential whole-body [¹⁸F]MFBG PET/CT up to 6 hours postinjection. Five controls and three PD patients underwent 120-min dynamic cardiac [¹⁸F]MFBG PET/CT and two static [¹²³I]MIBG SPECT/CT scans with planar scintigraphy, at 15 min and 3-4 h postinjection. An aortic image-derived input function with population-based radiometabolite corrections was validated against arterial sampling to derive myocardial distribution volume (V_T) using a 2-tissue compartment model (2TCM). [¹⁸F]MFBG V_Twas assessed for time-stability and compared to heart-to-mediastinum ratio (HMR) for [¹⁸F]MFBG and [¹²³I]MIBG. Mean effective dose was 23.1±2.6 μSv/MBq. [¹⁸F]MFBG exhibited rapid blood pool clearance and cardiac uptake, with V_T of 35.1±10.6 mL/cm3 in controls and 5.9±1.6 mL/cm3 in PD. 2TCM V_T from 30-min dynamic PET datasets starting at tracer injection showed strong agreement (mean difference -1.3 mL/cm3 and LoA=-7.1 mL/cm3 to 4.5 mL/cm3) and correlation (R2=0.97, p<0.001) to 2TCM V_T from full 120-min datasets. [¹⁸F]MFBG HMR correlated the same to [¹⁸F]MFBG V_T (ρ=0.88, p=0.007) for 10-30-min as for 100-120-min postinjection time intervals. [¹²³I]MIBG HMR correlated more strongly to [¹⁸F]MFBG V_T at 3-4h (ρ=0.9, p<0.005) compared to at 15-min (ρ=0.69, p=0.069) postinjection. [¹⁸F]MFBG PET is a feasible and safe imaging modality for non-invasive and simplified quantification of myocardial sympathetic innervation. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06120049.