11C-ER176, a Radioligand for 18-kDa Translocator Protein, Has Adequate Sensitivity to Robustly Image All Three Affinity Genotypes in Human Brain

Overview

Journal J Nucl Med

Specialty Nuclear Medicine

Date 2016 Nov 19

PMID 27856631

Citations 76

Authors

Masamichi Ikawa

Talakad G Lohith

Stal Shrestha

Sanjay Telu

Sami S Zoghbi

Sabrina Castellano

Sabrina Taliani

Federico Da Settimo

Masahiro Fujita

Victor W Pike

Robert B Innis

Affiliations

Soon will be listed here.

Abstract

Methods: Nine healthy volunteers-3 high-affinity binders (HABs), 3 mixed-affinity binders (MABs), and 3 low-affinity binders (LABs)-were studied with whole-body C-ER176 PET imaging. SUVs from 60 to 120 min after injection derived from each organ were compared between genotypes. Eight separate healthy volunteers-3 HABs, 3 MABs, and 2 LABs-underwent brain PET imaging. The 3 HABs underwent a repeated brain scan after TSPO blockade with XBD173 (N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-phenylpurin-9-yl)acetamide) to determine nondisplaceable distribution volume (V) via Lassen occupancy plotting and thereby estimate BP in brain.

Results: Regional SUV averaged from 60 to 120 min after injection in brain and peripheral organs with high TSPO densities such as lung and spleen were greater in HABs than in LABs. On the basis of V determined via the occupancy plot, the whole-brain BP for LABs was estimated to be 1.4 ± 0.8, which was much lower than that for HABs (4.2 ± 1.3) but about the same as that for HABs with C-PBR28 ([methyl-C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine)) (∼1.2).

Conclusion: Obvious in vivo sensitivity to rs6971 was observed in C-ER176 that had not been expected from in vitro studies, suggesting that the future development of any improved radioligand for TSPO should consider the possibility that in vitro properties will not be reflected in vivo. We also found that C-ER176 has adequately high BP for all rs6971 genotypes. Thus, the new radioligand would likely have greater sensitivity in detecting abnormalities in patients.

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