[18F]PR04.MZ PET/CT Imaging for Evaluation of Nigrostriatal Neuron Integrity in Patients With Parkinson Disease

Abstract

Introduction Degeneration of dopaminergic, nigrostriatal neurons is the hallmark of Parkinson disease (PD), and PET quantification of dopamine transporters is a widely accepted method for differential diagnosis between idiopathic PD and essential tremor. [18F]PR04.MZ is a new PET tracer with excellent imaging properties allowing for precise quantification of striatal and extrastriatal dopamine transporter. Here we describe our initial experience with [18F]PR04.MZ PET/CT in a larger cohort of healthy controls and PD patients as a proof-of-concept study for this tracer. Methods Eighteen healthy subjects, 19 early PD patients (Hoehn-Yahr I–II), and 13 moderate-advanced PD patients (Hoehn-Yahr III–IV) underwent static PET/CT scans 60 to 90 minutes after injection of 5.16 ± 1.03 mCi (191 ± 38 MBq) [18F]PR04.MZ. Specific binding ratios (SBRs) were calculated for caudate nucleus, anterior putamen, posterior putamen, substantia nigra (SNpc), compared between different groups and correlated with clinical ratings. Results [18F]PR04.MZ showed very high and specific uptake in the putamen, caudate, and substantia nigra pars compacta and very low nonspecific binding in other brain regions, and SBR values for the control group were 22.3 ± 4.1, 19.1 ± 3.5, and 5.4 ± 1.2, respectively. A reduction of SBR values was observed in all regions and in both initial and moderate PD, ranging from 35% to 89% (P < 0.001). The observed pattern of reduction was posterior putamen > anterior putamen > substantia nigra pars compacta > caudate, with contralateral posterior putamen being the most affected region. Rostrocaudal depletion gradient was evident in all PD patients and progression correlated with motor manifestations. Conclusions [18F]PR04.MZ PET/CT is a highly sensitive imaging modality for the detection of dopaminergic deficit in nigrostriatal pathways in PD.

Whole-body biodistribution and radiation dosimetry of [18F]PR04.MZ: a new PET radiotracer for clinical management of patients with movement disorders

“…F]PR04.MZ showed high specific uptake in striatal and midbrain regions [13] and showed very promising results for the evaluation of the dopaminergic, nigro-striatal integrity in patients with movement disorders such as Holmes Tremor [14] PS [15]. In combination with the excellent imaging properties, the dosimetry profile of [ 18 F]PR04.MZ supports clinical applications in larger groups of patients being evaluated for movement disorders.…”

“…This is within the standard range of 15–30 µSv/MBq observed for the majority of 18 F-labelled PET tracers and a standard injection of 185 MBq [ 18 F]PR04.MZ would result in an effective dose of approximately 3 mSv. In addition, [ 18 F]PR04.MZ showed high specific uptake in striatal and midbrain regions [ 13 ] and showed very promising results for the evaluation of the dopaminergic, nigro-striatal integrity in patients with movement disorders such as Holmes Tremor [ 14 ] PS [ 15 ]. In combination with the excellent imaging properties, the dosimetry profile of [ 18 F]PR04.MZ supports clinical applications in larger groups of patients being evaluated for movement disorders.…”

“…The pharmacokinetic evaluation of [ 18 F]PR04.MZ showed very high specific uptake in striatal and midbrain regions, excellent imaging contrast and robust quantification outcomes [ 13 ]. Following the clinical translation, the diagnostic potential of this new tracer was highlighted by the excellent imaging properties in a case study of Holmes Tremor [ 14 ] and the clinical validation for detection of nigro-striatal degeneration in patients under evaluation for movement disorders [ 15 ].…”

Prodromal manifestations of Parkinson’s disease in adults with 22q11.2 microdeletion syndrome

“…Dysautonomia was evaluated using the Composite Autonomic Symptom Score (COMPASS31) scale (Sletten et al, 2012)-The RBD-13 and the RBD-1Q screening questionnaires were answered by participants or caretakers living with them (Postuma, Arnulf, et al, 2012;Stiasny-Kolster et al, 2007). Integrity of dopaminergic neurons in nigrostriatal regions was evaluated by PET/CT imaging of DAT with 18 F-PR04.MZ, as previously described (Juri et al, 2021;Kramer et al, 2020;Lehnert et al, 2022).…”

The role of neuroimaging in Parkinson’s disease

“…This might be the reason why studies with [ 99m Tc]Tc-TRODAT-1 are mostly performed in Asia and South America (Ferraz, 2014;Hossein-Tehrani et al, 2020;Hwang et al, 2004;Sasannezhad et al, 2017;Sood et al, 2021). (Appel et al, 2015), 40-50 min for [ 18 F]PR04.MZ (Juri et al, 2021;Kramer, Juri, et al, 2020), >80 min for [ 11 C]RTI-32 (Guttman et al, 1997), and 3-4 h for [ 18 F]CFT (Laakso et al, 1998).…”