Comparative evaluation of two glycine transporter 1 radiotracers [11C]GSK931145 and [18F]MK‐6577 in baboons. Issue 3 (6th January 2016)

• Record Type: Journal Article
• Authors: Zheng, Ming‐Qiang; Lin, Shu‐Fei; Holden, Daniel; Naganawa, Mika; Ropchan, Jim R.; Najafzaden, Soheila; Kapinos, Michael; Tabriz, Mike; Carson, Richard E.; Hamill, Terence G.; Huang, Yiyun
• Is Part Of: Synapse. Volume 70:Issue 3(2016:Mar.)
• Page Start: 112
• Page End: 120
• Publication Date: 2016-01-06
• Subjects: PET imaging -- GlyT1 -- [11C]GSK931145 -- [18F]MK‐6577; Synapses -- Periodicals; 612
• DOI: 10.1002/syn.21879
• Languages: English
• ISSNs: 0887-4476

Abstract

Abstract : SUV images summed from 30 to 45 min post injection of [ 11 C]GSK931145 (A) and [ 18 F]MK‐6577 (B) in coronal (left), transverse (middle) and sagittal (right) views, along with co‐registered MR images (top). Both radiotracers showed good uptake and distribution profiles consistent with regional GlyT1 densities. ABSTRACT : Glycine transporter type‐1 (GlyT1) has been proposed as a target for drug development for schizophrenia. PET imaging with a GlyT1 specific radiotracer will allow for the measurement of target occupancy of GlyT1 inhibitors, and for in vivo investigation of GlyT1 alterations in schizophrenia. We conducted a comparative evaluation of two GlyT1 radiotracers, [ 11 C]GSK931145, and [ 18 F]MK‐6577, in baboons. Two baboons were imaged with [ 11 C]GSK931145 and [ 18 F]MK‐6577. Blocking studies with GSK931145 (0.3 or 0.2 mg/kg) were conducted to determine the level of tracer specific binding. [ 11 C]GSK931145 and [ 18 F]MK‐6577 were synthesized in good yield and high specific activity. Moderately fast metabolism was observed for both tracers, with ∼30% of parent at 30 min post‐injection. In the brain, both radiotracers showed good uptake and distribution profiles consistent with regional GlyT1 densities. [ 18 F]MK‐6577 displayed higher uptake and faster kinetics than [ 11 C]GSK931145. Time activity curves were well described by the two‐tissue compartment model. Regional volume of distribution ( V T ) values were higher for [ 18 F]MK‐6577 than [ 11 C]GSK931145. Pretreatment with GSK931145 reduced tracer uptake to a homogeneous level throughout the brain, indicating in vivo binding specificity and lack of a reference region for both radiotracers. Linear regression analysis of V T estimates between tracers indicated higher specific binding for [ 18 F]MK‐6577 than [ 11 C]GSK931145, consistent with higher regional binding potential ( BP ND ) values of [ 18 F]MK‐6577 calculated using V T from the baseline scans and non‐displaceable distribution volume ( V ND ) derived from blocking studies. [ 18 F]MK‐6577 appears to be a superior radiotracer with higher brain uptake, faster kinetics, and higher specific binding signals than [ 11 C]GSK931145.Synapse 70:112–120, 2016. © 2016 Wiley Periodicals, Inc.