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 - PubMed (original) (raw)

Comparative Study

. 2010 Feb 15;49(4):2924-32.

doi: 10.1016/j.neuroimage.2009.11.056. Epub 2009 Dec 4.

Masahiro Fujita, Yota Fujimura, Nobuyo Kimura, Kimberly J Jenko, Pavitra Kannan, Jinsoo Hong, Cheryl L Morse, Sami S Zoghbi, Robert L Gladding, Steven Jacobson, Unsong Oh, Victor W Pike, Robert B Innis

Affiliations

Comparative Study

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

William C Kreisl et al. Neuroimage. 2010.

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.

Copyright 2009. Published by Elsevier Inc.

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Figures

Figure 1

Figure 1

Human whole body images from one binder (left) and one non-binder (right). Subjects were scanned with both [11C]-(R)-PK 11195 (top) and [11C]PBR28 (bottom). Images were obtained 10 min after injection of radioligand. Color bars represent concentration of radioactivity corrected for body weight and injected dose of activity (standardized uptake values). Note that these values are underestimated since displayed images are averaged in the anterior-posterior dimension.

Figure 2

Figure 2

Human time-activity curves for heart for [11C]-(R)-PK 11195 (A) and [11C]PBR28 (B), and for lung for [11C]-(R)-PK 11195 (C) and [11C]PBR28 (D). For each radioligand, (•) denotes binders and (○) denotes non-binders. Error bars denote standard deviation.

Figure 3

Figure 3

Time-activity curves for heart (A) and lung (B) for two rhesus monkeys using [11C]-(R)-PK 11195 at baseline (•) and after pre-blockade with 5 mg/kg nonradioactive PBR28 (○). For clarity, error bars are not shown. Conc = concentration.

Figure 4

Figure 4

A. Brain time-activity curves for a rhesus monkey using [11C]-(R)-PK 11195 at baseline (•) and after pre-blockade with 5 mg/kg nonradioactive PBR28 (○). B. Plasma concentration of [11C]-(R)-PK 11195 at baseline (•) and after pre-blockade with nonradioactive PBR28 (○). Insert: Plasma concentration curve magnified to demonstrate peak concentrations in plasma in both baseline and pre-blocked conditions.

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