Huang, Y. Y., Ma, K. H., Tseng, T. W., Chou, T. K., Ng, H., Mirsalis, J. C., … & Shiue, C. Y. (2010). Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys. European journal of nuclear medicine and molecular imaging, 37(3), 545-555.
4-[18F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken.
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 μg/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 μg/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-[18F]-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.
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 μGy/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 μSv/MBq, respectively.
Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[18F]-ADAM is safe for use in human PET imaging studies.
Keywords: 4-[18F]-ADAM, Serotonin transporter imaging agent, Toxicity, Radiation dosimetry