title: A Novel PET Imaging Probe for the Detection and Monitoring of Translocator Protein 18 kDa Expression in Pathological Disorders.
abstract: 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-[(18)F]fluoroethoxy)phenyl)-6,8-dichloroimidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide ([(18)F]1; [(18)F]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, [(18)F]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 [(11)C]PBR28 (BPND 1.55 ± 0.41). [(18)F]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 [(18)F]CB251 is a promising TSPO PET imaging agent for neuroinflammation and TSPO-rich cancers.
authors: Department of Pharmacy - Drug Sciences, University of Bari "A. Moro", Bari, Italy.
authors: Mara
authors: M
authors: Perrone
authors: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors: Byung Seok
authors: BS
authors: Moon
authors: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.|Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
authors: Hyun Soo
authors: HS
authors: Park
authors: Department of Pharmacy - Drug Sciences, University of Bari "A. Moro", Bari, Italy.
authors: Valentino
authors: V
authors: Laquintana
authors: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors: Jae Ho
authors: JH
authors: Jung
authors: Department of Pharmacy - Drug Sciences, University of Bari "A. Moro", Bari, Italy.
authors: Annalisa
authors: A
authors: Cutrignelli
authors: Department of Pharmacy - Drug Sciences, University of Bari "A. Moro", Bari, Italy.
authors: Angela
authors: A
authors: Lopedota
authors: Department of Pharmacy - Drug Sciences, University of Bari "A. Moro", Bari, Italy.
authors: Massimo
authors: M
authors: Franco
authors: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.|Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
authors: Sang Eun
authors: SE
authors: Kim
authors: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.|Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon, Republic of Korea.
authors: Byung Chul
authors: BC
authors: Lee
authors: Department of Pharmacy - Drug Sciences, University of Bari "A. Moro", Bari, Italy.
authors: Nunzio
authors: N
authors: Denora
mesh_terms: D000081:Acetamides / Q000493:pharmacokinetics*; D000818:Animals; D049109:Cell Proliferation; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006574:Heterocyclic Compounds, 2-Ring / Q000493:pharmacokinetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C000613420:2-(2-(4-(2-fluoroethoxy)phenyl)-6,8-dichloroimidazo(1,2-a)pyridin-3-yl)-N,N-dipropylacetamide; D000081:Acetamides; C463819:Bzrp protein, mouse; D006574:Heterocyclic Compounds, 2-Ring; D019275:Radiopharmaceuticals; D018079:Receptors, GABA