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.

PET imaging of neuroendocrine tumours (NET) is well established for staging and therapy follow-up. The short half-life, increasing costs, and regulatory issues significantly limit the availability of approved imaging agents, such as [⁶⁸Ga]Ga-DOTA-TATE. Al[¹⁸F]F-NOTA-Octreotide provides a similar biodistribution and tumour uptake, can be produced on a large scale and may improve access to precision imaging. Here we prospectively compared the clinical utility of [⁶⁸Ga]Ga-DOTA-TATE and Al[¹⁸F]F-NOTA-Octreotide in the Latin-American population. Our results showed that in patients with stage IV NETs [⁶⁸Ga]Ga-DOTA-TATE presents higher physiological uptake than Al[¹⁸F]F-NOTA-Octreotide in the liver, hypophysis, salivary glands, adrenal glands (all p < 0.001), pancreatic uncinated process, kidneys, and small intestine (all p < 0.05). Nevertheless, despite the lower background uptake of Al[¹⁸F]F-NOTA-Octreotide, comparative analysis of tumour-to-liver (TLR) and tumour-to-spleen (TSR) showed no statistically significant difference for lesions in the liver, bone, lymph nodes, and other tissues. Only three discordant lesions in highly-metastases livers were detected by [⁶⁸Ga]Ga-DOTA-TATE but not by Al[¹⁸F]F-NOTA-Octreotide and only one discordant lesion was detected by Al[¹⁸F]F-NOTA-Octreotide but not by [⁶⁸Ga]Ga-DOTA-TATE. Non-inferiority analysis showed that Al[¹⁸F]F-NOTA-Octreotide is comparable to [⁶⁸Ga]Ga-DOTA-TATE. Hence, our results demonstrate that Al[¹⁸F]F-NOTA-Octreotide provided excellent image quality, visualized NET lesions with high sensitivity and represents a highly promising, clinical alternative to [⁶⁸Ga]Ga-DOTA-TATE.