title: Click synthesis and biologic evaluation of (R)- and (S)-2-amino-3-[1-(2-[18F]fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid for brain tumor imaging with positron emission tomography.
abstract: The (R)- and (S)-enantiomers of 2-amino-3-[1-(2-[18F]fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid (4) were synthesized and evaluated in the rat 9L gliosarcoma brain tumor model using cell uptake assays, biodistribution studies, and micro-positron emission tomography (microPET). The (R)- and (S)-enantiomers of [18F]4 were radiolabeled separately using the click reaction in 57% and 51% decay-corrected yields, respectively. (S)-[18F]4 was a substrate for cationic amino acid transport and, to a lesser extent, system L transport in vitro. In vivo biodistribution studies demonstrated that (S)-[18F]4 provided higher tumor uptake and higher tumor to brain ratios (15:1 at the 30- and 60-minute time points) compared to the (R)-enantiomer (7:1 at the 30- and 60-minute time points). MicroPET studies with (S)-[18F]4 confirmed that this tracer provides good target to background ratios for both subcutaneous and intracranial 9L gliosarcoma tumors. Based on these results, the 1H-[1,2,3]triazole-substituted amino acid (S)-[18F]4 has promising PET properties for brain tumors and represents a novel class of radiolabeled amino acids for tumor imaging.
authors.affiliation: Department of Radiology (Radiologic Sciences), Washington University School of Medicine, St. Louis, MO 63110, USA. mcconathyj@mir.wustl.edu
authors.forename: Jonathan
authors.initials: J
authors.lastname: McConathy
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.forename: Stephany E
authors.initials: SE
authors.lastname: Shockley
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Jones
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Griffin
authors.forename: Hsiaoju
authors.initials: H
authors.lastname: Lee
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Adams
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001932:Brain Neoplasms / Q000097:blood / Q000000981:diagnostic imaging*; D057930:Click Chemistry / Q000379:methods*; D018316:Gliosarcoma / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D049268:Positron-Emission Tomography / Q000379:methods*; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D040521:Subcutaneous Tissue / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: C558631:2-amino-3-(1-(2-fluoroethyl)-1H-(1,2,3)triazol-4-yl)propanoic acid; D011422:Propionates; D014230:Triazoles; D000409:Alanine