title: Nitriles form mixed-coligand complexes with (99m)Tc-HYNIC-peptide.
abstract: Using a 12-amino acid peptide conjugated with HYNIC as a model, we investigated nitriles as possible coligands for labeling with (99m)Tc. After the preparation of the (99m)Tc labeled HYNIC-peptide using tricine as coligand, the addition of acetonitile was found by reverse phase HPLC to block further coligand exchange with ethylenediamine diacetic acid (EDDA) at room temperature. The addition of this nitrile changed the pharmacokinetics of the (99m)Tc labeled peptide in normal mice towards faster clearance and significant differences in accumulation in most tissues sampled. By replacing acetonitrile with cyanoacetate, a nitrile not present in the HPLC eluant, it was possible to show the existence of a new, more hydrophilic, species by reverse phase HPLC. We conclude that nitriles can act as coligands for HYNIC-conjugated peptides labeled with (99m)Tc and tricine. Furthermore, the presence of acetonitrile during Sep-Pak or HPLC purification may inadvertently generate a mixed tricine/acetonitile coligand (99m)Tc-HYNIC-peptide complex.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Guozheng
authors.initials: G
authors.lastname: Liu
authors.forename: Charles
authors.initials: C
authors.lastname: Wescott
authors.forename: Aaron
authors.initials: A
authors.lastname: Sato
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Zhang
authors.forename: Mary
authors.initials: M
authors.lastname: Rusckowski
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Hnatowich
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006834:Hydrazines / Q000737:chemistry / Q000493:pharmacokinetics*; D051379:Mice; D009539:Nicotinic Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D009570:Nitriles / Q000737:chemistry / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: C120392:6-hydrazinopyridine-3-carboxylic acid; D000097:Acetonitriles; D006834:Hydrazines; D009539:Nicotinic Acids; D009570:Nitriles; D015609:Organotechnetium Compounds; C032159:acetonitrile