title: Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: PET Center, Department of Nuclear Medicine, Tri-Service General Hospital, 325 Sec. 2, Cheng-Kung Rd., Neihu 114, Taipei, Taiwan.
authors.forename: Ya-Yao
authors.initials: YY
authors.lastname: Huang
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Ma
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Tseng
authors.forename: Ta-Kai
authors.initials: TK
authors.lastname: Chou
authors.forename: Hanna
authors.initials: H
authors.lastname: Ng
authors.forename: Jon C
authors.initials: JC
authors.lastname: Mirsalis
authors.forename: Ying-Kai
authors.initials: YK
authors.lastname: Fu
authors.forename: Tieh-Chi
authors.initials: TC
authors.lastname: Chu
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Huang
authors.forename: Chyng-Yann
authors.initials: CY
authors.lastname: Shiue
mesh_terms: D000328:Adult; D000818:Animals; D001596:Benzylamines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity*; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D000882:Haplorhini; D006801:Humans; D008297:Male; D011829:Radiation Dosage; D011869:Radioligand Assay; D011874:Radiometry; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D001596:Benzylamines; D005462:Fluorine Radioisotopes; C475911:N,N-dimethyl-2-(2-amino-4-fluorophenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins