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Pet radiotracers for imaging fatty acid metablolism and storage

A technology of fatty acids and radioisotopes, applied in the direction of in vivo radioactive preparations, preparation of X-ray contrast agents, preparations for in vivo experiments, etc.

Inactive Publication Date: 2012-04-18
UNIV OF WASHINGTON
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the effects of changes in plasma matrix, workload, and blood flow on myocardial dynamics are unknown

Method used

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  • Pet radiotracers for imaging fatty acid metablolism and storage
  • Pet radiotracers for imaging fatty acid metablolism and storage
  • Pet radiotracers for imaging fatty acid metablolism and storage

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0211] Example 1: Imaging of small animals.

[0212] Animal preparation. All animal procedures were performed in compliance with the guidelines for the care and use of animals established by the Washington University Animal Research Committee. Animal preparation was performed as previously described. 24-26 . Mice were placed in metabolic cages and anesthetized by inhalation of 2%-2.5% isoflurane in an induction chamber. Anesthesia was maintained throughout imaging with 1%-1.5% isoflurane delivered through a custom-made nose cone. Venous access is via the exopharyngeal vein. Body temperature is maintained with circulating water blankets and heat lamps. Monitor heart and respiration rates throughout the procedure.

[0213] PET collection. Animals were secured in custom-made acrylic restraints and placed within the field of view of the small animal imaging PET scanner. Imaging acquisition was started 5 s after the tracer was injected via the right jugular catheter. Imagi...

Embodiment 2

[0215] Example 2: Large animal imaging.

[0216] Animal preparation. Purpose-bred ~6-10 kg male Beagle dogs were fasted, anesthetized and instrumented as previously described 3，4 . One femoral vein is catheterized for dosing. For arterial samples, a catheter was placed in the thoracic aorta through the femoral artery and arterial blood pressure was monitored. To obtain a venous blood pressure sample, a coronary sinus cannula can be placed through the right external jugular vein under fluoroscopic guidance as previously described 28 . ECG, arterial blood pressure and heart rate can be detected throughout the process. All measurements can be performed on the microPET Focus 220. All procedures were performed in accordance with the guidelines for the care and use of research animals.

[0217] PET imaging protocol. Two imaging schemes can be used.

[0218] plan 1. Transmission scans were initially used to correct for positron decay. After a transmission scan, perform a 5...

Embodiment 3

[0221] This example shows the flexibility of our strategy, initially comparing the 60 min kinetics of the 2-fluoroethoxy analogue for IPPA to that in the same animal ( Figure 4 )of 11 C-palmitate ( Figure 4 ) kinetic comparison. Imaging for both radiotracers was 60 min. use 11 C-palmitate (top) and with 18 Composite myocardial microPET images of fed mice studied with F-FAA-labeled novel fatty acid analogs (bottom). Images are shown from the horizontal axis and present data obtained 20-30 min after tracer injection. 18 F-FAA Image Ratio 11 The C-palmitate image shows excellent quality and high tracer activity. Figure 4 Individual microPET images are presented. The top rows (18-13330 and 19-12011) are 11 C-palmitate image and the top rows (18-22135 and 19-21952) are 18 F-FAA image. Increasing signal strength is indicated by green to yellow to red (highest). Relatively similar tracer kinetics were noted ( Figure 5 ).

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Abstract

Fatty acid analogue ( FAA) molecules comprising positron-emitting radionuclides, salts thereof, and FAA-triglycerides are disclosed Also disclosed are methods of synthesis, and methods of imaging distribution and metabolism of fatty acids and fatty acid triglycerides.

Description

[0001] priority statement [0002] This application claims the benefit of and priority to US Provisional Application No. 61 / 175,065, filed May 4, 2009, which is hereby incorporated by reference in its entirety. [0003] governmental support [0004] This work was supported at least in part by NIH grant HL69100. The Government may have certain rights in this invention. Background technique [0005] The present invention relates to the field of tracers useful for imaging fatty acid and fatty acid triglyceride distribution and metabolism. [0006] The distribution of fatty acids, including complexes of fatty acids (FA) and triglycerides, (FA-TG), in various tissues, such as myocardial tissue, plays a very important clinical role. [0007] Various probes and methods have been proposed for imaging the distribution of fatty acids in a subject, eg, the human body. [0008] 31 P and 13 C NMR spectroscopy (MRS) has been used to visualize myocardial substrate metabolism in in vivo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/00
CPCC07B59/00C07C59/64C07D249/04C07C51/09A61K51/0402C07C59/68C07C53/132C07C53/15A61K49/04
Inventor 罗伯特·H·马赫罗伯特·约翰·格勒普尔屠朱德皮拉尔·赫雷罗
Owner UNIV OF WASHINGTON
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