Radiation dosimetry of [(18)F]VAT in nonhuman primates

BACKGROUND: The objective of this study is to determine the radiation dosimetry of a novel radiotracer for vesicular acetylcholine transporter (−)-(1-((2R,3R)-8-(2-[(18)F]fluoro-ethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone ([(18)F]VAT) based on PET imaging in nonhuman primates. [(18)F]VAT has potential for investigation of neurological disorders including Alzheimer’s disease, Parkinson’s disease, and dystonia. METHODS: Three macaque fascicularis (two males, one female) received 185.4–198.3 MBq [(18)F]VAT prior to whole-body imaging in a MicroPET-F220 scanner. Time activity curves (TACs) were created from regions of interest (ROIs) that encompassed the entire small organs or samples with the highest activity within large organs. Organ residence times were calculated based on the TACs. We then used OLINDA/EXM 1.1 to calculate human radiation dose estimates based on scaled organ residence times. RESULTS: Measurements from directly sampled arterial blood yielded a residence time of 0.30 h in agreement with the residence time of 0.39 h calculated from a PET-generated time activity curve measured in the left ventricle. Organ dosimetry revealed the liver as the critical organ (51.1 and 65.4 μGy/MBq) and an effective dose of 16 and 19 μSv/MBq for male and female, respectively. CONCLUSIONS: The macaque biodistribution data showed high retention of [(18)F]VAT in the liver consistent with hepatobiliary clearance. These dosimetry data support that relatively safe doses of [(18)F]VAT can be administered to obtain imaging in humans.