Nitriles form mixed-coligand complexes with (99m)Tc-HYNIC-peptide.
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.
Liu
Guozheng
G
Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Wescott
Charles
C
Sato
Aaron
A
Wang
Yi
Y
Liu
Ning
N
Zhang
Yu-Min
YM
Rusckowski
Mary
M
Hnatowich
Donald J
DJ
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
C120392:6-hydrazinopyridine-3-carboxylic acid; D000097:Acetonitriles; D006834:Hydrazines; D009539:Nicotinic Acids; D009570:Nitriles; D015609:Organotechnetium Compounds; C032159:acetonitrile