Synthesis and biodistribution of a novel ~(99m)Tc complex of HYNIC-conjugated metronidazole as a potential tumor hypoxia imaging agent

摘要

A conjugate of 6-hydrazinopyridine-3-carboxylic acid (HYNIC) with the amino analogue of metronidazole (MN) was synthesized through a multiple-step reaction. HYNIC-MN could be labeled easily and efficiently with ~(99m)Tc using N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) and ethylenediamine -N,N′-diacetic acid (EDDA) as coligands to form the ~(99m)Tc-HYNIC-MN complex in high yield (>95%). Its partition coefficient indicated that it was a good hydrophilic complex. The tumor cell experiment showed that the ~(99m)Tc-HYNIC-MN complex had a certain hypoxic selectivity. The biodistribution studies of ~(99m)Tc-HYNIC-MN in Kunming mice bearing S180 tumor showed a favorable tissue distribution profile with high tumor uptake, and low or negligible accumulation in non-target organs, suggesting ~(99m)Tc-HYNIC-MN would be a novel potential tumor hypoxia imaging agent.