Preparation And Biodistribution Of ～(99m)Tc Labeled Compounds For Imaging Tumor Hypoxia

Malignant tumors are fatal illnesses that threaten people's life severely. In solid malignant tumors, a malignant tumor require nutrition and oxygen for their growth. It is a pity that abnormal structure and function of vessels bring about decreased supply of oxygen to tumor. A hypoxic region will occur when cells obtain insufficient supply of oxygen. It is confirmed that tumor hypoxia can resist radiotherapy and many chemotherapy. In addition, tumor hypoxia can profoundly affect the malignation process of cancerous cells. Therefore, exploring the hypoxic extent of tumor cells is very important. Of so mang methods for exploring the hypoxic extent of tumor cells, nuclear medicine technology offers a non-invasive and widely available clinical method for demonstrating tumor hypoxia, since hypoxia imaging can detect the position and number of hypoxia tissues. With this information, doctors can adopt optimal treatment to improve the efficiency of radio- and chemo- therapy.The study of hypoxia imaging agents has been a hotspot in the fields of radiopharmaceuticals. Early interest centered around nitroimidazole and non-nitroimidazole compounds labeled with 82Br 18F,123I,131I,99mTc,62Cu,60Cu or 64Cu. Among these radiopharmaceuticals, I8F-MISO,123I-IAZA,99mTc-HL91,BMS194796 and BMS181321 have shown selectivity in hypoxic cells. However, these agents presented sever non-specific accumulations in normal tissues and organs in vivo that decreased their sensitivity and accuracy as tumor hypoxia imaging agents.The chelating agents synthesized were l-N-[2-(2-Nitro-lH- imidazolyl)ethyl- amine]-l,2-propanedione Dioxime (2NI-EHPED) and l-N-[2-(4- Nitro-lH-imida-zolyl)ethylamine]-l,2-propanedione Dioxime (4NI-EHPED). The ligands were characterized by melting point, mass spectrometry, and nuclear magnetic resonance. The results confirmed that they are the desired compounds.The labeling of the two ligands was carried out at room temperature with radiochemical purity of approximately 90% for [99mTc0](2NI-EHPED)2and 94% for [99mTc0](4NI-EHPED)2, as were evaluated by paper and thin-layer chromatography.The biodistribution results showed a quicker clearance rate for [99mTcO](2NI-EHPED)2over that of [99mTc0](4NI-EHPED)2; and a greater %ID/g for [99mTc0](2NI-EHPED)2 than that of [99mTc0](4NI-EHPED)2, suggesting that the 2-NI label might have selective uptake in tumor.In summary, two amine oximes containing nitroimidazole chelating agents were successfully synthesized, characterized and labeled with 99mTc. The labeled 2-NI componds showed selective accumulation in xenografted H22 tumors. The results warranted a further investigation and development of tumor hypoxia selective imaging agents of 99mTc, 186Re/188Re, and 64Cu/67Cu labeled 2-NI chelating agents. Key words: hypoxia imaging agents, 99mTc, chelates, 2-nitroimidazole, tumor.