UNLABELLED: 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. Copyright 2009. Published by Elsevier Inc.
UNLABELLED: 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. Copyright 2009. Published by Elsevier Inc.
Authors: M C Petit-Taboué; J C Baron; L Barré; J M Travère; D Speckel; R Camsonne; E T MacKenzie Journal: Eur J Pharmacol Date: 1991-08-06 Impact factor: 4.432
Authors: Vassilios Papadopoulos; Mario Baraldi; Tomás R Guilarte; Thomas B Knudsen; Jean-Jacques Lacapère; Peter Lindemann; Michael D Norenberg; David Nutt; Abraham Weizman; Ming-Rong Zhang; Moshe Gavish Journal: Trends Pharmacol Sci Date: 2006-07-05 Impact factor: 14.819
Authors: C Ferrarese; I Appollonio; M Frigo; M Perego; R Piolti; M Trabucchi; L Frattola Journal: Acta Psychiatr Scand Date: 1990-08 Impact factor: 6.392
Authors: C G Lee; M M Gottesman; C O Cardarelli; M Ramachandra; K T Jeang; S V Ambudkar; I Pastan; S Dey Journal: Biochemistry Date: 1998-03-17 Impact factor: 3.162
Authors: Masahiro Fujita; Masao Imaizumi; Sami S Zoghbi; Yota Fujimura; Amanda G Farris; Tetsuya Suhara; Jinsoo Hong; Victor W Pike; Robert B Innis Journal: Neuroimage Date: 2007-11-22 Impact factor: 6.556
Authors: Peter S Bloomfield; Sudhakar Selvaraj; Vincenzo de Paola; Oliver D Howes; Mattia Veronese; Gaia Rizzo; Alessandra Bertoldo; David R Owen; Michael Ap Bloomfield; Ilaria Bonoldi; Nicola Kalk; Federico Turkheimer; Philip McGuire Journal: Am J Psychiatry Date: 2015-10-16 Impact factor: 18.112
Authors: Hye-Yeong Kim; Ran Li; Thomas S C Ng; Gabriel Courties; Christopher Blake Rodell; Mark Prytyskach; Rainer H Kohler; Mikael J Pittet; Matthias Nahrendorf; Ralph Weissleder; Miles A Miller Journal: ACS Nano Date: 2018-12-11 Impact factor: 15.881
Authors: Unsong Oh; Masahiro Fujita; Vasiliki N Ikonomidou; Iordanis E Evangelou; Eiji Matsuura; Erin Harberts; Yota Fujimura; Nancy D Richert; Joan Ohayon; Victor W Pike; Yi Zhang; Sami S Zoghbi; Robert B Innis; Steven Jacobson Journal: J Neuroimmune Pharmacol Date: 2010-09-25 Impact factor: 4.147
Authors: Paolo Zanotti-Fregonara; Mattia Veronese; Belen Pascual; Robert C Rostomily; Federico Turkheimer; Joseph C Masdeu Journal: Eur J Nucl Med Mol Imaging Date: 2019-01-17 Impact factor: 9.236
Authors: Michael Benatar; Kevin Boylan; Andreas Jeromin; Seward B Rutkove; James Berry; Nazem Atassi; Lucie Bruijn Journal: Muscle Nerve Date: 2015-12-29 Impact factor: 3.217