PET imaging of the brain serotonin transporters (SERT) with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) in humans: a preliminary study.
OBJECTIVE
The aim of this study was to assess the feasibility of using 4-[(18)F]-ADAM as a brain SERT imaging agent in humans.


METHODS
Enrolled in the study were 19 healthy Taiwanese subjects (11 men, 8 women; age 33 ± 9 years). The PET data were semiquantitatively analyzed and expressed as specific uptake ratios (SUR) and distribution volume ratios (DVR) using the software package PMOD. The SUR and DVR of 4-[(18)F]-ADAM in the raphe nucleus (RN), midbrain (MB), thalamus (TH), striatum (STR) and prefrontal cortex (PFC) were determined using the cerebellum (CB) as the reference region.


RESULTS
4-[(18)F]-ADAM bound to known SERT-rich regions in human brain. The order of the regional brain uptake was MB (RN) > TH > STR > PFC > CB. The DVR (n = 4, t* = 60 min) in the RN, TH, STR and PFC were 3.00 ± 0.50, 2.25 ± 0.45, 2.05 ± 0.31 and 1.40 ± 0.13, respectively. The optimal time for imaging brain SERT with 4-[(18)F]-ADAM was 120-140 min after injection. At the optimal imaging time, the SURs (n = 15) in the MB, TH, STR, and PFC were 2.25 ± 0.20, 2.28 ± 0.20, 2.12 ± 0.18 and 1.47 ± 0.14, respectively. There were no significant differences in SERT availability between men and women (p < 0.05).


CONCLUSIONS
The results of this study showed that 4-[(18)F]-ADAM was safe for human studies and its distribution in human brain appeared to correlate well with the known distribution of SERT in the human brain. In addition, it had high specific binding and a reasonable optimal time for imaging brain SERT in humans. Thus, 4-[(18)F]-ADAM may be feasible for assessing the status of brain SERT in humans.
Department of Nuclear Medicine, PET Center, Tri-Service General Hospital, 325 Sec. 2 Cheng-Kung Rd, Neihu, Taipei, Taiwan.
Wen-Sheng
WS
Huang
San-Yuan
SY
Huang
Pei-Shen
PS
Ho
Kuo-Hsing
KH
Ma
Ya-Yao
YY
Huang
Chin-Bin
CB
Yeh
Ren-Syuan
RS
Liu
Cheng-Yi
CY
Cheng
Chyng-Yann
CY
Shiue
D000328:Adult; D001596:Benzylamines / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000032:analysis*; D014018:Tissue Distribution
D001596:Benzylamines; C475911:N,N-dimethyl-2-(2-amino-4-fluorophenylthio)benzylamine; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins