Novel technetium-99m-labeled higher fatty acid derivative

Abstract

The invention relates to a novel technetium-99m-labeled higher fatty acid derivative. The derivative is characterized in that tricarbonyl technetium coordinates with higher fatty acid cyclopentadiene, and the fatty acid connected with cyclopentadiene comprises carbonyl group and unsaturated cyclic group. The derivative can be used as a myocardium imaging agent, and can solve the defects of high liver background or high blood background existing in the prior art when the existing technetium-99mm-labeled higher fatty acid derivative is applied to the myocardium imaging agent; and therefore, the novel technetium-99m-labeled higher fatty acid derivative which has low liver background and low blood background, and can be clinically used as the myocardium imaging agent is provided.

Description

technical field [0001] The present invention relates to a higher fatty acid derivative. Specifically, it is a new technetium-99m labeled higher fatty acid derivative. Background technique [0002] Cardiovascular and cerebrovascular diseases, including heart disease, high blood pressure, and hyperlipidemia, have become the main diseases that endanger people's health. In the prevention and treatment of heart disease, radiopharmaceuticals play an important role in the early diagnosis of heart disease. In the myocardium, fatty acids release energy through oxidation and decomposition. The myocardial metabolic imaging agent labeled with radioactive elements can be used to locate myocardial ischemia, measure changes reflecting myocardial metabolic function, detect myocardial cell survival, etc., thus providing a reliable basis for clinical diagnosis of cardiovascular diseases. [0003] Radiopharmaceuticals based on positron emission tomography PET / single photon emission computeri...

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Problems solved by technology

[0005] In 2006, the journal "Isotopes" published the paper "Long-chain fatty acid derivatives 99m Tc-MAMA-(CH2) n Preparation and Biodistribution of COOH", in which Professor Wang Xuebin from Beijing Normal University synthesized a series of technetium-99m core-labeled long-chain fatty acid derivatives using short-chain diacids and MAMA ligands as starting materials[ 99m Tc]-MAMA-(CH 2 ) n COOH (n=14,15,16,17) The biodistribution data of normal mice showed that the uptake percentages of such markers in the myocardium at 5 minutes were 5.73%ID / g, 5.52%ID / g, 4.82%ID / g, 4.03%ID / g (%ID / g g is the percentage of the radiopharmaceutical per gram of tissue in the total injection dose), but the blood uptake of radiopharmaceuticals is higher than that of the myocardium, that is, the blood background is high, and the blood clearance is slow, so it is not suitable as a myocardium. image agent for application

[0006] In the journal Applied Radiation and Isotopes in 2008, Chu Taiwei and others passed [ 99m Tc(CO) 3 (H 2 O) 3 ] + complexation of the core with fatty acid ligands to obtain 99m Tc(CO) 3 -IUA and 99m Tc(CO) 3 -BPIUA Unfortunately, these two compounds, like other technetium-labeled fatty acid analogues, show a high blood / heart ratio in vivo distribution studies in mice, that is, the blood uptake of radiopharmaceuticals is higher than the uptake of radiopharmaceuticals by the myocardium, so These two compounds are not suitable for use in myocardial imaging studies

[0007] In the journal Journal of Medicinal Chemistry in 2007, the document Technetium-99m-labeled long chain fatty acid analogues metabolized by β-oxidation in the heart was disclosed, in which Yasushi Arano et al first reported the use of [ 99m Tc]CpTT-PA Myocardial fatty acid metabolism was measured, and myocardial metabolism experiments showed that 67% of the [ 99m Tc]CpTT-PA was absorbed, achieving a high myocardial uptake, but after 10 minutes, the uptake in the myocardium was 1.87% ID / g, the uptake in the liver was 7.56% ID / g, and the radiopharmaceutical uptake in the liver The amount is higher than that of the myocardium, that is, a higher liver background is formed, which is not conducive to the imaging of the myocardium

[0008] In 2008, the journal Journal of Medicinal Chemistry disclosed the document 16-Cyclopentadienyl Tricarbonyl Tc16-Oxo-hexadecanoic Acid: Synthesis and Evaluation of Fatty Acid Metabolism in Mouse Myocardium, wherein, Yearn Seong Choe et al. 99m On the basis of the structure of Tc]CpTT-PA, the carbonyl group connected to the pentadiene ring was retained, and the compound [ 99m Tc]-CpTT-16-oxo-HAD Animal experiments show that: the myocardial uptake is higher than [ 99m Tc]CpTT-PA has increased, but the liver uptake reached 25.6%ID / g in 1 minute, and the liver background is high, which directly affects the imaging of the myocardium

[0009] Therefore, in the prior art, the advantages of technetium-99m-labeled higher fatty acid imaging agents are high myocardial initial uptake and rapid myocardial metabolism; but The metabolism of technetium-99m-labeled advanced fatty acid myocardial imaging agents in the liver or in the blood is slow, forming a high liver background or blood background, thus affecting myocardial imaging

Therefore, no technetium-99m-labeled advanced fatty acid imaging agent has entered the clinical trial stage

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