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

• Published in: European journal of nuclear medicine and molecular imaging 2010-03, Vol.37 (3), p.545-555
• Main Authors: Huang, Ya-Yao, Ma, Kuo-Hsing, Tseng, Ta-Wei, Chou, Ta-Kai, Ng, Hanna, Mirsalis, Jon C., Fu, Ying-Kai, Chu, Tieh-Chi, Huang, Wen-Sheng, Shiue, Chyng-Yann
• Format: Article
• Language: English
• Subjects: Adult; Animals; Benzylamines - chemistry; Benzylamines - metabolism; Benzylamines - pharmacokinetics; Benzylamines - toxicity; Cardiology; Dosimetry; Female; Fluorine Radioisotopes - chemistry; Haplorhini; Humans; Imaging; Male; Medical imaging; Medicine; Medicine & Public Health; Nuclear Medicine; Oncology; Original Article; Orthopedics; Radiation Dosage; Radiation therapy; Radioligand Assay; Radiology; Radiometry; Rats; Serotonin; Serotonin Plasma Membrane Transport Proteins - metabolism; Tissue Distribution; Toxicity
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-009-1281-z

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 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-[ 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 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. 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.