Initial human PET studies with [18F]PR04.MZ for quantification of striatal and extrastriatal dopamine transporters

Objectives The dopamine transporter (DAT) is considered to be a valuable target for preclinical detection of neurodegenerative diseases and its availability correlates with striatal dopamine concentration and clinical severity of Parkinson’s disease. Herein we report initial human PET studies with [18F]PR04.MZ, a high affine and selective DAT ligand for quantification of dopamine transporters.

Methods 3 Healthy male subjects (mean age 47 a) underwent a dynamic PET scan (Siemens mCT) for a duration of 2 h after bolus injection of 165 ± 15 MBq (mean ± SD) [18F]PR04.MZ. Data analysis using noninvasive SRTM method and cerebellum as reference was performed for estimation of binding potential in different brain regions.

Results Highest tracer uptake was observed in putamen and caudate nucleus after 25 minutes followed by slow washout. Tissue-to-cerebellum ratio in putamen, caudate nucleus and midbrain region reached a maximum of about 23.5, 21.5 and 5 after 75, 70 and 45 minutes, respectively and remained nearly constant till end of scan. BPnd determined using SRTM method were 16 ± 0.3, 14 ± 1.5 and 2.6 ± 0.3 (mean ± SD), respectively. Main excretion pathways were urinary and gastrointestinal elimination as determined by whole-body scan 2 h after injection and bone uptake of 18F-fluoride as main metabolite was observed.

Conclusions [18F]PR04.MZ showed a relatively fast kinetic and very high specific uptake in DAT rich regions in the human brain and seems to be a promising tool for striatal and extrastriatal DAT quantification. Although it has been shown that noninvasive SRTM may be applied for data analysis this still has to be proved by comparison with invasive methods and is part of current studies.