Cardiac Sympathetic Neuroimaging in Autonomic Synucleinopathies: ¹²³I-Metaiodobenzylguanidine and ¹⁸F-Dopamine

In the diagnostic evaluation of Parkinson's disease (PD), cardiac sympathetic neuroimaging has been viewed as a supportive test. This review argues that the clinical and scientific value of cardiac sympathetic neuroimaging is broader than being merely confirmatory. ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) single photon emission computed tomography (SPECT) is the practical clinical modality for detecting cardiac sympathetic denervation, whereas ¹⁸F-dopamine positron emission tomography (PET) also provides a pathophysiologic probe of sympathetic neuronal uptake, vesicular sequestration, and intra-neuronal catecholamine metabolism. In autonomic synucleinopathies, this distinction is especially relevant for separating PD with orthostatic hypotension (PD + OH) from the parkinsonian form of multiple system atrophy (MSA-P), for predicting phenoconversion in isolated neurogenic OH, for delineating specific intra-neuronal functional abnormalities, and for stratifying patients for mechanism-based treatment trials. Evidence from prospective longitudinal studies and computational modeling supports a body-first pathway in some central Lewy body diseases, with cardiac noradrenergic deficiency preceding overt motor or cognitive manifestations. Cardiac sympathetic neuroimaging therefore may help move the field from clinical confirmation toward biomarker-based diagnosis, prognostication, and preclinical intervention.