Comparison of [(11)C]-(R)-PK 11195 and [(11)C]PBR28, two radioligands for translocator protein (18 kDa) in human and monkey: Implications for positron emission tomographic imaging of this inflammation biomarker.
Ten percent of humans lack specific binding of [(11)C]PBR28 to 18 kDa translocator protein (TSPO), a biomarker for inflammation. "Non-binders" have not been reported using another TSPO radioligand, [(11)C]-(R)-PK 11195, despite its use for more than two decades. This study asked two questions: (1) What is the cause of non-binding to PBR28? and (2) Why has this phenomenon not been reported using [(11)C]-(R)-PK 11195?


METHODS
Five binders and five non-binders received whole-body imaging with both [(11)C]-(R)-PK 11195 and [(11)C]PBR28. In vitro binding was performed using leukocyte membranes from binders and non-binders and the tritiated versions of the ligand. Rhesus monkeys were imaged with [(11)C]-(R)-PK 11195 at baseline and after blockade of TSPOs.


RESULTS
Using [(11)C]PBR28, uptake in all five organs with high densities of TSPO (lung, heart, brain, kidney, and spleen) was 50% to 75% lower in non-binders than in binders. In contrast, [(11)C]-(R)-PK 11195 distinguished binders and non-binders in only heart and lung. For the in vitro assay, [(3)H]PBR28 had more than 10-fold lower affinity to TSPO in non-binders than in binders. The in vivo specific binding of [(11)C]-(R)-PK 11195 in monkey brain was approximately 80-fold lower than that reported for [(11)C]PBR28.


CONCLUSIONS
Based on binding of [(3)H]PK 11195 to leukocyte membranes, both binders and non-binders express TSPO. Non-binding to PBR28 is caused by its low affinity for TSPO in non-binders. Non-binding may be differentially expressed in organs of the body. The relatively low in vivo specific binding of [(11)C]-(R)-PK 11195 may have obscured its detection of non-binding in peripheral organs.
Kreisl
William C
WC
Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA. kreislw@mail.nih.gov
Fujita
Masahiro
M
Fujimura
Yota
Y
Kimura
Nobuyo
N
Jenko
Kimberly J
KJ
Kannan
Pavitra
P
Hong
Jinsoo
J
Morse
Cheryl L
CL
Zoghbi
Sami S
SS
Gladding
Robert L
RL
Jacobson
Steven
S
Oh
Unsong
U
Pike
Victor W
VW
Innis
Robert B
RB
D000081:Acetamides / Q000493:pharmacokinetics*; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D000882:Haplorhini; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging* / Q000378:metabolism*; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018079:Receptors, GABA / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D051598:Whole Body Imaging / Q000379:methods
D000081:Acetamides; D015415:Biomarkers; D002250:Carbon Radioisotopes; D007546:Isoquinolines; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; C037850:PK 11195