Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys.
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.
Huang
Ya-Yao
YY
PET Center, Department of Nuclear Medicine, Tri-Service General Hospital, 325 Sec. 2, Cheng-Kung Rd., Neihu 114, Taipei, Taiwan.
Ma
Kuo-Hsing
KH
Tseng
Ta-Wei
TW
Chou
Ta-Kai
TK
Ng
Hanna
H
Mirsalis
Jon C
JC
Fu
Ying-Kai
YK
Chu
Tieh-Chi
TC
Huang
Wen-Sheng
WS
Shiue
Chyng-Yann
CY
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
D001596:Benzylamines; D005462:Fluorine Radioisotopes; C475911:N,N-dimethyl-2-(2-amino-4-fluorophenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins