PT  - JOURNAL ARTICLE
AU  - Nabulsi, Nabeel
AU  - Holden, Daniel
AU  - Hamill, Terence
AU  - Lin, Shu-fei
AU  - Gao, Hong
AU  - Fowles, Krista
AU  - Labaree, David
AU  - Carson, Richard
AU  - Huang, Yiyun
TI  - Comparative evaluation of the histamine 3 receptor (H<sub>3</sub>R) radiotracers <sup>11</sup>C-MK-8278 and <sup>11</sup>C-GSK189254
DP  - 2014 May 01
TA  - Journal of Nuclear Medicine
PG  - 320--320
VI  - 55
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/55/supplement_1/320.short
4100  - http://jnm.snmjournals.org/content/55/supplement_1/320.full
SO  - J Nucl Med2014 May 01; 55
AB  - 320 Objectives The central H3R is a presynaptic autoreceptor regulating release of histamine, and is implicated in a variety of disorders. 11C-GSK189254 [1] and 11C-MK-8278 [2] are PET radiotracers for H3R imaging. The aim of this study is to compare the imaging properties of these tracers in baboons. Methods PET scans were acquired for 2 h on the HR+ scanner in two baboons with arterial sampling and metabolite analysis. Brain regional time-activity curves (TACs) were analyzed with 1-tissue (1T) and 2-tissue (2T) compartmental models to estimate volumes of distribution (VT). Data from preblocking scans with MK-8278 were analyzed using occupancy plots. Results Metabolism of 11C-MK-8278 (n = 4) was fast, with ~ 40% of parent remaining at 30 min after tracer injection compared with ~80% for 11C-GSK189254 (n = 4). Plasma free fraction was high for both tracers (0.57 for 11C-MK-8278 and 0.68 for 11C-GSK189254). In the brain, 11C-MK-8278 displayed fast kinetics (regional activity peaked at ~20 min) while that for 11C-GSK189254 was protracted (activity uptake plateaued at the end of the 2 h scan). Regional TACs fitted well with the 1T model. Mean VT values were 28.8, 26.6, 23.5, 19.0, 18.3, 13.4, 11.2, 9.3, and 8.4 mL/cm3 for 11C-MK-8278 in the nucleus accumbens, globus pallidus, putamen, cingulate cortex, caudate, frontal cortex, occipital cortex, pons, and brainstem, and 79.9, 65.9, 71.7, 60.5, 52.2, 44.1, 37.3, 27.6, and 25.1 mL/cm3 for 11C-GSK189254 in the same regions. Comparison of VT values suggests higher affinity for 11C-GSK189254 and comparable specific binding fractions. Pre-treatment with MK-8278 (0.5 mg/kg) gave receptor occupancy of 97% as measured by 11C-MK-8278, and 96% as measured by 11C-GSK189254. Conclusions Both 11C-MK-8278 and 11C-GSK189254 provide good specific binding and can be used for receptor occupancy study of H3R ligands, while the faster kinetics of 11C-MK-8278 may allow more reliable quantification of H3R alterations in humans. Research Support Yale PET Center pilot funding.