RESUMO
[18F]FluorTriopride ([18F]FTP) is a dopamine D3-receptor preferring radioligand with potential for investigation of neuropsychiatric disorders including Parkinson disease, dystonia and schizophrenia. Here we estimate human radiation dosimetry for [18F]FTP based on the ex-vivo biodistribution in rodents and in vivo distribution in nonhuman primates. Biodistribution data were generated using male and female Sprague-Dawley rats injected with ~370 KBq of [18F]FTP and euthanized at 5, 30, 60, 120, and 240 min. Organs of interest were dissected, weighed and assayed for radioactivity content. PET imaging studies were performed in two male and one female macaque fascicularis administered 143-190 MBq of [18F]FTP and scanned whole-body in sequential sections. Organ residence times were calculated based on organ time activity curves (TAC) created from regions of Interest. OLINDA/EXM 1.1 was used to estimate human radiation dosimetry based on scaled organ residence times. In the rodent, the highest absorbed radiation dose was the upper large intestines (0.32-0.49 mGy/MBq), with an effective dose of 0.07 mSv/MBq in males and 0.1 mSv/MBq in females. For the nonhuman primate, however, the gallbladder wall was the critical organ (1.81 mGy/MBq), and the effective dose was 0.02 mSv/MBq. The species discrepancy in dosimetry estimates for [18F]FTP based on rat and primate data can be attributed to the slower transit of tracer through the hepatobiliary track of the primate compared to the rat, which lacks a gallbladder. Out findings demonstrate that the nonhuman primate model is more appropriate model for estimating human absorbed radiation dosimetry when hepatobiliary excretion plays a major role in radiotracer elimination.
RESUMO
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.