Labeled 99mTc hydrazino-nicotinamide-dioxodecoyl-folic acid coordination compound and preparation method

Abstract

The invention discloses a labeled 99mTc hydrazino-nicotinamide-dioxodecoyl-folic acid coordination compound with a general formula of 99mTc(HYNIC-NOON-FA)(Tricine)(L). In the structural formula, L is triphenyl sodium phosphate or triphenyl sodium photrisulfonic acid, wherein 1,8-diamido-3,6-octane dioxide is used as a connecting chain for generating a hydrazino-nicotinamide-3,6-dioxodecoyl-folic acid coupler respectively with folic acid and hydrazino-niacin through amido bonds and coordinating with oxygen atoms and phosphorus atoms in a co-ligand Tricine and an L molecule and 99mTc, and the 99mTc(HYNIC-NOON-FA)(Tricine)(L) coordination compound is obtained through two steps of: (a) synthesizing the hydrazino-nicotinamide-3,6-dioxodecoyl-folic acid coupler used as a ligand; and (b) labeling the 99mTc-hydrazino-nicotinamide-dioxodecoyl-folic acid coordination compound. The coordination compound has the advantages of high radiochemical purity, good stability, high tumor intake, good retention, low non-target organ background and clear tumor SPECT (Single Photon Emission Computed Tomography) development and can be prepared into a novel 99mTc labeled folic acid receptor tumor developer widely applied to the technical field of radioactive pharmaceutical chemistry and nuclear medicine.

Description

Technical field [0001] The present invention relates to 99m The field of Tc-labeled radiopharmaceutical chemistry and clinical nuclear medicine technology, specifically relates to a 99m Tc labeled hydrazinonicotinyl-dioxoctanoyl-folate complex and its preparation method. Background technique [0002] The folate receptor is a glycoprotein linked to the cell membrane by the polysaccharide phosphatidylinositol, mainly including three subtypes of α, β and γ / γ′. Folate receptors, especially α-folate receptors, are highly expressed in many malignant tumors derived from epithelial tissues, such as ovarian cancer, breast cancer, endometrial cancer, lung cancer, nasopharyngeal cancer and other tumor cells, while in normal Expression is highly conserved in tissues. Folate receptors have high affinity and specificity for folate analogs such as folic acid, methotrexate, and 5-methyltetrahydrofolate, and can mediate the endocytosis of these substances into cells. Using this character...

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Problems solved by technology

Literature report 99m Tc-HYNIC-folate has good target-to-non-target ratios such as tumor / blood, tumor / meat, etc., but the absolute tumor uptake value in the KB tumor-bearing mouse model is low, and the background of liver, spleen, etc. is high ( W. Guo, G. H. Hinkle, R. J. Lee, 99m Tc-HYNIC-folate: a novel receptor-based targeted radiopharmaceutical for tumor imaging. J Nucl Med 1999; 40: 1563-1569; Liu Liqin, Wang Shizhen, etc. Folate receptor tumor imaging agent 99m Synthesis and animal imaging of Tc-hydrazinyl nicotinamide hydrazide-folic acid. Chinese Academy of Medical Sciences Journal. 2006; 28:786-789 Chinese Academy of Medical Sciences Journal)

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