Phosphine-containing HYNIC derivatives as potential bifunctional chelators for (99m)Tc-labeling of small biomolecules.
Two prototype phosphine-containing HYNIC chelators, HYNIC-Kp-DPPB and HYNIC-Ko-DPPB (HYNIC = 6-hydrazinonicotinamide; K = lysine; and DPPB = diphenylphosphine-benzoic acid), have been synthesized and characterized by NMR ((1)H, (13)C, and (31)P) and LC-MS. Macrocyclic (99m)Tc complexes, [(99m)Tc(HYNIC-Ko-TPPB)(tricine)] and [(99m)Tc(HYNIC-Kp-DPPB)(tricine)], were prepared by reacting the phosphine-containing HYNIC chelator with (99m)TcO(4)(-) in the presence of excess tricine and stannous chloride. Results from this study clearly demonstrated that both HYNIC-Kp-DPPB and HYNIC-Ko-DPPB are able to form highly stable macrocyclic (99m)Tc complexes, [(99m)Tc(HYNIC-Ko-TPPB)(tricine)] and [(99m)Tc(HYNIC-Kp-DPPB)(tricine)], when tricine is used as the coligand. Radio-HPLC data suggest that the complex [(99m)Tc(HYNIC-Kp-DPPB)(tricine)] exists as only one detectable isomer in solution while the complex [(99m)Tc(HYNIC-Ko-DPPB)(tricine)] has three isomers. It was also found that three isomers of [(99m)Tc(HYNIC-Ko-DPPB)(tricine)] interconvert at elevated temperatures, suggesting that the presence of these isomers might be due conformational changes in the macrocyclic Tc chelate. The LC-MS data for both macrocyclic (99m)Tc complexes are completely consistent with the proposed composition. The phosphine-containing HYNIC chelators described in this study may have the potential as bifunctional chelators for (99m)Tc labeling of small biomolecules.
Purohit
Ajay
A
Discovery Chemistry, Bristol-Myers Squibb Medical Imaging, 331 Treble Cove Road, North Billerica, Massachusetts 01862, USA.
Liu
Shuang
S
Casebier
Dave
D
Edwards
D Scott
DS
D002851:Chromatography, High Pressure Liquid; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D006834:Hydrazines / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D008956:Models, Chemical; D015394:Molecular Structure; D009539:Nicotinic Acids / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010720:Phosphines / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013997:Time Factors; D017971:Tin Compounds / Q000737:chemistry
C120392:6-hydrazinopyridine-3-carboxylic acid; D006834:Hydrazines; D008024:Ligands; D009539:Nicotinic Acids; D015609:Organotechnetium Compounds; D010720:Phosphines; D019275:Radiopharmaceuticals; D017971:Tin Compounds; C023599:stannous chloride; C044646:phosphine; D005998:Glycine; C100184:tricine