Synthesis and biodistribution of a novel ^99mTc complex of HYNIC-conjugated metronidazole as a potential tumor hypoxia imaging agent

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 Tc-99m using N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) and ethylenediamine -N,N'-diacetic acid (EDDA) as coligands to form the Tc-99m-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 Tc-99m-HYNIC-MN complex had a certain hypoxic selectivity. The biodistribution studies of Tc-99m-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 Tc-99m-HYNIC-MN would be a novel potential tumor hypoxia imaging agent.