Bioorganic & Medicinal Chemistry 2006-12-01

Evaluation of 99mTc(CO)3 complex of 2-methyl-5-nitroimidazole as an agent for targeting tumor hypoxia.

Madhava B Mallia, Suresh Subramanian, Sharmila Banerjee, H D Sarma, Meera Venkatesh

Index: Bioorg. Med. Chem. 14(23) , 7666-70, (2006)

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Abstract

An iminodiacetic acid (IDA) derivative of 2-methyl-5-nitroimidazole was synthesized as a carrier molecule for radiolabeling with the gamma emitting radioisotope, 99mTc, for imaging hypoxic regions of tumors. The ligand was synthesized in excellent yield and labeled using freshly prepared [99mTc(CO)3(H2O)3]+ intermediate. A complexation yield of over 95% could be achieved under mild conditions using a ligand concentration of 1 mg/mL [ approximately 3 x 10(-3)M]. The complex was characterized by HPLC and its stability in human serum was studied. Biodistribution studies performed in Swiss mice bearing fibrosarcoma tumor showed maximum accumulation in the tumor to the extent of approximately 0.52 % ID/g at 30 min post-injection (pi). The major clearance of the complex was through the hepatobiliary route. The complex showed tumor/muscle ratio of 1.75 at 30 min pi, which significantly increased to 17 at 180 min pi. However, the tumor/blood ratio was below one throughout the period of study, which could be due to slow clearance of the complex from blood.