Biodistribution and radiation dosimetry of [11C]DASB in baboons.
OBJECTIVE
The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [(11)C]DASB ([(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [(11)C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry.


METHODS
Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183+/-5 MBq/2.3+/-1.0 nmol of [(11)C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units.


RESULTS
Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6 x 10(-2) mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies.


CONCLUSIONS
Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [(11)C]DASB. In the United States, the absorbed dose to the lungs would limit [(11)C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female.
Bélanger
Marie-José
MJ
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Simpson
Norman R
NR
Wang
Theodore
T
Van Heertum
Ronald L
RL
Mann
J John
JJ
Parsey
Ramin V
RV
D000814:Aniline Compounds / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009928:Organ Specificity; D010215:Papio; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014915:Whole-Body Counting
C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides