title: 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.
abstract: 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.
authors: Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA. kreislw@mail.nih.gov
authors: William C
authors: WC
authors: Kreisl
authors: Masahiro
authors: M
authors: Fujita
authors: Yota
authors: Y
authors: Fujimura
authors: Nobuyo
authors: N
authors: Kimura
authors: Kimberly J
authors: KJ
authors: Jenko
authors: Pavitra
authors: P
authors: Kannan
authors: Jinsoo
authors: J
authors: Hong
authors: Cheryl L
authors: CL
authors: Morse
authors: Sami S
authors: SS
authors: Zoghbi
authors: Robert L
authors: RL
authors: Gladding
authors: Steven
authors: S
authors: Jacobson
authors: Unsong
authors: U
authors: Oh
authors: Victor W
authors: VW
authors: Pike
authors: Robert B
authors: RB
authors: Innis
mesh_terms: 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
chemical_list: 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