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Pendant fatty acid imaging agents

Inactive Publication Date: 2010-09-09
MOLECULAR INSIGHT PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0041]In another aspect the disclosure provides methods for using imaging agents to identify a lesion. In an embodiment, the lesion is in a cardiovascular system. In an exemplary embodiment, the detection of the lesion may be used in diagnosing or effectively treating myocardial infarction, unstable angina, heart failure, and ischemic myocardium. In an embodiment, the compounds of the instant disclosure have high specificity for the myocardium when administered to a subject in vivo.

Problems solved by technology

Identifying which patients are actually having a heart attack and require hospitalization can be challenging.
As pointed out in the NIH's 1997 National Heart Attack Alert Program Report on Diagnostic Technologies for Acute Cardiac Ischemia, there have been no diagnostic tests to-date that have been shown by controlled clinical trials to improve emergency room decision-making in actual practice.
In ischemia, when blood flow is diminished under stress, the heart lacks an adequate supply of oxygen to utilize fatty acids efficiently.
However, none of the omega labeled fatty acids have been shown to trace fatty acid metabolism, while some had either low heart-to-blood ratios and others exhibited low uptake in the myocardium.

Method used

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  • Pendant fatty acid imaging agents
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  • Pendant fatty acid imaging agents

Examples

Experimental program
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Effect test

example 1

Synthesis of [99mTc(CO)3η3-(Fatty Acid PAMA or Cp)] Derivatives

[0148]Carbon monoxide is flushed for 20 minutes into a sealed vial containing 18 mg each of Na2CO3 and NaBH4. Added to the pressurized vial is 1 ml of TcO4− and the solution is heated at 100° C. for 30 minutes. After cooling the solution, formation of [Tc(CO)3(H2O)3(H2O)3]+ is examined by HPLC. The [Tc(CO)3(H2O)3]+ elutes at 3 minutes while unreacted TcO4− has a retention time of 8 minutes. Utilizing the method described for the synthesis of [99 mTc(CO)3(H2O)3]+, 2 mg of the appropriate fatty acid derivative is added to the dry vial before introducing the Na2CO3 and NaBH4. The mixture is incubated at 100° C. for 30 minutes, whereupon it is filtered and analyzed via HPLC for product yield and purity.

example 2

Synthesis of [99mTcO-(Fatty Acid MAMA)] Derivatives

[0149]Preparation of the Tc-99m-labeled MAMA and DADT derivatized fatty acid complexes is achieved by adding 500 ul of a Tc-99m-glucoheptate kit (Dupont) to a solution of the appropriate derivatized fatty acid (2 mg / 100 ul methanol) and 100 ul of DMSO. The mixture is incubated at 100° C. for 30 minutes, whereupon it is filtered through a Millipore Millex-GV 0.22 μm filter and analyzed via HPLC for product yield and purity. The radioactive product(s) elutes at >18 minutes.

example 3

Preparation of C18 Pendant PAMA

[0150]Methyl 9-(1-bromopropane)octadecanoate (0.6 g, 1.4 mmol), N-(2-methyl acetate) 2-aminomethylpyridine (0.42 g, 2.1 mmol), and potassium carbonate (0.05 g) were stirred in DMF (10 mL) at 110-120 C for 2 hrs. The mixture was diluted with methylene chloride (50 mL) washed with water (3×) and dried. Chromatography on silica gel (95:5 hexane / ethyl acetate) afforded 0.3 g (43%) of the diester.

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Abstract

The disclosure provides pendant fatty acid compounds for use in diagnostic imaging, (particularly the cardiovascular system), as well as kits comprised of the same. The disclosure also provides for a method administering a imaging agent with a high specificity for the myocardium.

Description

RELATED APPLICATION INFORMATION[0001]This application is a continuation application of and claims priority to and the benefit of U.S. patent application Ser. No. 10 / 405,094 filed on Apr. 1, 2003, which claims priority to U.S. Provisional Patent Application No. 60 / 368,933 filed Apr. 1, 2002, the entire teachings of which are incorporated herein by reference.BACKGROUND[0002]Every year, seven million Americans arrive in emergency rooms complaining of chest pain indicating a possible heart attack. Identifying which patients are actually having a heart attack and require hospitalization can be challenging. More than 40% of emergency room chest pain patients, estimated at more than 3 million, are admitted to hospitals unnecessarily at an estimated annual cost of $10-$13 billion. These unnecessary hospitalizations may be avoided if better diagnostic tests existed for emergency room use. As pointed out in the NIH's 1997 National Heart Attack Alert Program Report on Diagnostic Technologies f...

Claims

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Application Information

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IPC IPC(8): C07F13/00A61K51/00A61K51/04
CPCA61K51/0402C07F13/005A61K51/0487A61K51/0478
Inventor BABICH, JOHN W.
Owner MOLECULAR INSIGHT PHARMA