Synthesis and biodistribution of a novel 99mTc complex of HYNIC-conjugated metronidazole as a potential tumor hypoxia imaging agent
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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 99mTc using N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) and ethylenediamine -N,N′-diacetic acid (EDDA) as coligands to form the 99mTc–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 99mTc–HYNIC–MN complex had a certain hypoxic selectivity. The biodistribution studies of 99mTc–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 99mTc–HYNIC–MN would be a novel potential tumor hypoxia imaging agent.
Keywords99mTc HYNIC Bifunctional chelator Hypoxia imaging agent Metronidazole
The work was financially supported by the Fundamental Research Funds for the Central Universities of China (FRF-BR-09-006A) and by the International Science and Technology Cooperation Program of China (ISTCP) (2008AR), the Ministry of Science and Technology of the People’s Republic of China. The radiochemical data were acquired at Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education. The authors thank Dr. Zhang Shijian for his help with the animal experiments.
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