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Novel technetium-99m-labeled higher fatty acid derivative

A high-grade fatty acid, -99m technology, applied in the field of high-grade fatty acid derivatives, can solve the problems of unfavorable myocardial imaging, slow blood clearance, slow metabolism, etc.

Inactive Publication Date: 2012-01-11
BEIJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

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 [99mTc(CO)3 (H2O)3]+The core is coordinated with the fatty acid ligand to obtain 99mTc(CO)3-IUA and 99mTc(CO)3-BPIUA Unfortunately, these two compounds are the same as other technetium-labeled fatty acid analogs, distribution studies in mice Indicates a high blood / heart ratio, i.e. blood uptake of radiopharmaceuticals is higher than myocardial uptake of radiopharmaceuticals, therefore these two compounds are not suitable for myocardial imaging studies
[0007] In the 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, among which Yasushi Arano et al. It is the first report to use [99mTc]CpTT-PA to measure myocardial fatty acid metabolism. 67% of the [99mTc]CpTT-PA that entered the heart was absorbed, achieving a high myocardial uptake, but after 10 minutes, the myocardial uptake was 1.87%ID / g, and the liver uptake The amount of radiopharmaceuticals was 7.56%ID / g, and the uptake of radiopharmaceuticals in the liver was higher than that in the myocardium, which formed a higher liver background, which was not conducive to 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

Method used

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  • Novel technetium-99m-labeled higher fatty acid derivative
  • Novel technetium-99m-labeled higher fatty acid derivative
  • Novel technetium-99m-labeled higher fatty acid derivative

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074]

[0075] Compound 1: 15-cyclopentadienyltricarbonyltechnetium-15-carbonylpentadecanoyl-5-thiophene-2-acetic acid ( 99m Tc-CpTTOPTAA)

[0076] The compound one ( 99m The synthetic route of Tc-CpTTOPTAA) is:

[0077]

[0078] The synthetic steps of described compound one are:

[0079] (1) Under ice bath conditions, dilute 15 mL of freshly distilled SOCl 2 Slowly add it dropwise to 11mmol pentadecanoyl acid. After the dropwise addition, continue to stir for 10 minutes, then raise the temperature to 90°C, and reflux for 12 hours. The following reaction occurs to generate the product pentadecanoyl chloride. After the reaction, the excess SOCl was evaporated 2 , the product is directly reacted in the next step without further purification; step (1) corresponds to the following reaction formula:

[0080]

[0081] (2) Add 15 mL of anhydrous dichloromethane to the product obtained in step (1) to dissolve to obtain a dichloromethane solution of pentadecanoyl chlori...

Embodiment 2

[0099]

[0100] Compound 2: 17-cyclopentadienyltricarbonyltechnetium-17-carbonylheptadecanoyl-5-furan-2-acetic acid ( 99m Tc-CpTTOPFAA)

[0101] The compound two ( 99m The synthetic route of Tc-CpTTOPFAA) is:

[0102]

[0103] The synthetic steps of described compound two are:

[0104] (1) Under the condition of ice bath, put 15mL freshly distilled SOCl 2 Slowly add it dropwise to 11 mmol of heptadecanoic acid. After the dropwise addition, continue to stir for 10 minutes, then raise the temperature to 80-90°C, and reflux for 6-12 hours. The following reaction occurs to generate the product heptadecanoyl chloride. After the reaction, the excess SOCl was evaporated 2 , the product was directly reacted in the next step without further purification. Step (1) corresponds to the following reaction:

[0105]

[0106] (2) Add 15mL of anhydrous dichloromethane to the product obtained in step (1) to dissolve to obtain a dichloromethane solution of seventeen-acioyl chlori...

Embodiment 3

[0115]

[0116] Compound 3: 17-cyclopentadienyltricarbonyltechnetium-17-carbonylheptadecanoyl-5-(N-methyl)pyrrole-2-acetic acid

[0117] ( 99m Tc-CpTTOPMPAA)

[0118] The compound three ( 99m The synthetic route of Tc-CpTTOPMPAA) is:

[0119]

[0120] The synthetic steps of described compound three are:

[0121] (1) Under the condition of ice bath, put 15mL freshly distilled SOCl 2 Slowly add dropwise to 11mmol heptadecanoic acid, after the dropwise addition, continue to stir for 10min, then raise the temperature to 80-95°C, reflux for 6-12 hours, the following reaction occurs, and the product heptadecanoyl chloride is generated; after the reaction, Evaporate excess SOCl 2 , the product is directly reacted in the next step without further purification; step (1) corresponds to the following reaction formula:

[0122]

[0123] (2) Add 15mL of anhydrous dichloromethane to the product obtained in step (1) to dissolve to obtain a dichloromethane solution of seventeen...

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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...

Claims

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Application Information

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IPC IPC(8): C07F13/00A61K51/00A61K103/10
Inventor 张华北曾华辉于海静
Owner BEIJING NORMAL UNIVERSITY
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