title: MBC94, a conjugable ligand for cannabinoid CB 2 receptor imaging.
abstract: Cannabinoid CB 2 receptor is a particularly attractive target for noninvasive imaging of neuroinflammation and monitoring of therapeutic efficacy. Its expression is low to undetectable in healthy brain and induced in resident microglial cells (the macrophage of the brain) after cerebral ischemia, injury, and in neuroinflammatory disease. Additionally, immune cells migrating across the blood-brain barrier typically express CB 2 receptors, which adds to the expression pool of this target and provides a reliable indicator of inflammation in the brain. Here, we synthesized a novel conjugable CB 2 receptor ligand, mbc94, which has a terminal amino group that allows for facile conjugation to imaging moieties. A near-infrared (NIR) dye labeled mbc94, NIRmbc94, was developed for CB 2 targeted imaging. Preliminary evidence, including in vitro fluorescence imaging and a competition study, showed that NIRmbc94 specifically labeled CB 2-expressing cells.
authors.affiliation: Department of Chemistry, Vanderbilt University, VU Station B 351822, Nashville, Tennessee 37235-1822, USA.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Bai
authors.forename: Michelle
authors.initials: M
authors.lastname: Sexton
authors.forename: Nephi
authors.initials: N
authors.lastname: Stella
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: Bornhop
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000378:metabolism*; D001667:Binding, Competitive; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001892:Camphanes / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001952:Bridged-Ring Compounds; D001892:Camphanes; D005456:Fluorescent Dyes; D008024:Ligands; C532005:MBC94; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528