A Novel PET Imaging Probe for the Detection and Monitoring of Translocator Protein 18 kDa Expression in Pathological Disorders

作者：Perrone Mara; Moon Byung Seok; Park Hyun Soo; Laquintana Valentino; Jung Jae Ho; Cutrignelli Annalisa; Lopedota Angela; Franco Massimo; Kim Sang Eun; Lee Byung Chul^*; Denora Nunzio^*

来源：Scientific Reports, 2016, 6(1): 20422.

DOI：10.1038/srep20422

A new fluorine-substituted ligand, compound 1 (CB251), with a very high affinity (Ki = 0.27 +/- 0.09 nM) and selectivity for the 18-kDa translocator protein (TSPO), is presented as an attractive biomarker for the diagnosis of neuroinflammation, neurodegeneration and tumour progression. To test compound 1 as a TSPO PET imaging agent in vivo, 2-(2-(4-(2-[F-18]fluoroethoxy)phenyl)-6,8-dichloroimidazo[1,2-a]pyridin-3-yl)-N, N-dipropylacetamide ([F-18]1; [F-18]CB251) was synthesized by nucleophilic aliphatic substitution in a single-step radiolabelling procedure with a 11.1 +/- 3.5% (n = 14, decay corrected) radiochemical yield and over 99% radiochemical purity. In animal PET imaging studies, [F-18]CB251 provided a clearly visible image of the inflammatory lesion with the binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND 1.83 +/- 0.18), in a neuroinflammation rat model based on the unilateral stereotaxic injection of lipopolysaccharide (LPS), comparable to that of [C-11]PBR28 (BPND 1.55 +/- 0.41). [F-18]CB251 showed moderate tumour uptake (1.96 +/- 0.11%ID/g at 1 h post injection) in human glioblastoma U87-MG xenografts. These results suggest that [F-18]CB251 is a promising TSPO PET imaging agent for neuroinflammation and TSPO-rich cancers.