Preparation method and application for 99mTc-labelled hydrazino-nicotinamide-5-aminopentanoic acid-pteroyl lysine complex

Abstract

The invention discloses a 99mTc-labelled hydrazino-nicotinamide-5-aminopentanoic acid-pteroyl lysine complex having an expression of 99mTc(HYNIC-penta-lys-Pteroyl) (Tricine / TPPTS), as well as a preparation method and an application, wherein the target complex is obtained by preparation comprising the following two steps: step a, synthesising a ligand, namely, pteroyl lysine-5-aminopentanoic acid-6-(2-N,N-dimethyl benzaldehyde hydrazono) nicotinic acid; and step b, preparing the 99mTc-labelled hydrazino-nicotinamide-5-aminopentanoic acid-pteroyl lysine complex. The complex has the advantages of being high in radiochemical purity, good in stability, low in price, high in tumour uptake, good in retention, and high in target / non-target ratios such as tumour / blood ratio and tumour / liver ratio, and can be popularized and applied as a novel 99mTc-labelled folate receptor tumour developer.

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 Preparation method and application of Tc-labeled hydrazinyl nicotinamide-5-aminovaleric acid-pteroyl lysine complex. Background technique [0002] Folic Acid, aka Vitamin B 9 , is an indispensable substance for eukaryotic cells to proliferate and synthesize DNA, because it can provide a 1-carbon source as an auxiliary factor for DNA synthesis. Normally, there are three different ways that cells use folic acid uptake. Under physiological conditions, normal cells transport folate analogs mainly through membrane diffusin, reduced folate carrier, and proton-to-folate transporter. Among them, the proton-to-folate transporter is highly expressed in the duodenum and jejunum, and it also chooses to be transported under lower pH conditions. The reduced folate carrier has a low affinity for oxidiz...

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Problems solved by technology

However, the uptake of non-target organs such as the heart, liver, and lungs is also very high, and the target-to-non-target ratio is not ideal (Hongjuan Guo, Fang Xie, Meilin Zhu, Yan Li, Zhi Yang, Xuebin Wang, Jie Lu.The synthesis of Pteroyl -lys co nj ugates and its application as Technetium-99m labeled radiotracer for folate receptor-positive tumor targeting. Bioorg. Med. Chem. Lett. 2011, 21, 2025-2029)

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