Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-(18F)-ADAM in rats and monkeys.

摘要

PURPOSE: 4-[(18)F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken. METHODS: Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected intravenously with 4-F-ADAM as a single dose of 1,023.7 microg/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 microg/kg (100 times the human dose). PET/CT scans were performed in seven Formosa Rock monkeys (four males and three females) using a Siemens Biograph scanner. After injection of 4-[(18)F]-ADAM (182+/-8 MBq), a low dose CT scan and a series of eight whole-body PET scans were performed. Whole-body images were acquired in 3-D mode. Time-activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using OLINDA/EXM software. RESULTS: In the rats neither the single dose nor the five daily doses of 4-F-ADAM produced overt adverse effects clinically. In the monkeys the radiation doses received by most organs ranged between 7.1 and 35.7 microGy/MBq, and the urinary bladder was considered to be the critical organ. The effective doses extrapolated to male and female adult humans were 17.4 and 21.8 microSv/MBq, respectively. CONCLUSION: Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[(18)F]-ADAM is safe for use in human PET imaging studies.