title: Synthesis and in vivo evaluation of (11) C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl}amide.
abstract: Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers because of their hydrophobic character, spherical structure, and excellent chemical and photochemical stability. In the present paper, the synthesis and in vivo evaluation of (11) C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl}amide, an analog of the D2 receptor ligand [(11) C]raclopride, is described. The radiosynthesis was approached by reaction of the demethylated precursor with [(11) C]CH3 I in basic media; moderate radiochemical yields (18.2 ± 2.8%, decay corrected), and excellent radiochemical purities (>98%) were obtained in overall synthesis time of ~50 min. In vivo assays showed a biodistribution pattern with significant uptake in liver, kidneys and lungs at short times (t = 4 min) after administration and increasing accumulation in bladder at longer times (t ≥ 14.5 min). Although brain positron emission tomography scans showed good blood brain barrier penetration, the high unspecific uptake observed in different brain regions impedes its applicability as D2 receptor ligand.
authors.affiliation: Radiochemistry Department, Molecular Imaging Unit, CIC biomaGUNE; Parque Tecnológico de Miramón, San Sebastián, Guipúzcoa, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gómez-Vallejo
authors.forename: Naiara
authors.initials: N
authors.lastname: Vázquez
authors.forename: Kiran Babu
authors.initials: KB
authors.lastname: Gona
authors.forename: Maria
authors.initials: M
authors.lastname: Puigivila
authors.forename: Mikel
authors.initials: M
authors.lastname: González
authors.forename: Eneko San
authors.initials: ES
authors.lastname: Sebastián
authors.forename: Abraham
authors.initials: A
authors.lastname: Martin
authors.forename: Jordi
authors.initials: J
authors.lastname: Llop
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D060326:Chemistry Techniques, Synthetic; D008297:Male; D049268:Positron-Emission Tomography; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D000577:Amides; D001896:Boron Compounds; D002250:Carbon Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2
keywords: PET; carbon-11; dicarba-closo-dodecaboranes; dopamine; raclopride; receptor