Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28: a PET radioligand to image inflammation.
(11)C-PBR28 ([methyl-(11)C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine) is a recently developed radioligand to image peripheral benzodiazepine receptors (PBRs) in brain. The aim of this study was to estimate the human radiation doses of (11)C-PBR28 based on biodistribution data in monkeys and humans. In addition, we scanned 1 human subject who fortuitously behaved as if he lacked the PBR binding protein.


METHODS
Whole-body PBR images were acquired after intravenous bolus administration of (11)C-PBR28 in 7 healthy humans (651 +/- 111 MBq) and 2 rhesus monkeys (370 +/- 59.9 MBq). One monkey was scanned after receptor blockade with PK 11195 (10.7 mg/kg intravenously).


RESULTS
For typical subjects (subjects 1-6), the 3 organs with highest exposure were those with the high PBR densities (kidneys, spleen, and lungs), and the effective dose was 6.6 microSv/MBq. The unusual subject (subject 7) had 60%-90% less uptake in these 3 organs, resulting in 28% lower effective dose. The activity in the baseline monkey scans was greater than that in humans for organs with high PBR densities. For this reason, the human effective dose was overestimated by 60% with monkey biodistribution data. The monkey with receptor blockade had an overall distribution qualitatively similar to that of the unusual human subject (subject 7), with decreased exposure to lungs, kidney, and spleen.


CONCLUSIONS
The effective dose of (11)C-PBR28 was modest and was similar to that of several other (11)C-radioligands. Lack of receptor binding in the unusual human subject and in the monkey with receptor blockade decreased exposure to organs with high PBR densities and enhanced uptake in excretory and metabolic pathways.
Brown
Amira K
AK
Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland 20892-2035, USA. amirabrown@mail.nih.gov
Fujita
Masahiro
M
Fujimura
Yota
Y
Liow
Jeih-San
JS
Stabin
Michael
M
Ryu
Yong H
YH
Imaizumi
Masao
M
Hong
Jinsoo
J
Pike
Victor W
VW
Innis
Robert B
RB
D000328:Adult; D000818:Animals; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011743:Pyrimidines / Q000493:pharmacokinetics*; D011829:Radiation Dosage; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D018079:Receptors, GABA / Q000032:analysis*; D013045:Species Specificity; D014018:Tissue Distribution
C526315:(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; C037850:PK 11195