We are developing 99mTc-Glucarate as a diagnostic radiopharmaceutical for use in molecular imaging of both the heart and certain tumors. This compound has been shown to localize in various tumors as well as in necrotic myocardial and cerebral tissue. The lead indication for 99mTc-Glucarate is that of rapid detection of equivocal acute myocardial infarction. This agent is currently in phase II clinical trials for this indication. We also are developing 99mTc-Glucarate for the detection of breast tumors adjunctive to mammography. For this indication the agent is named BTSCAN.
Our glucarate product is supplied as a lyophilized formulation in a 10 mL vial. It is labeled with 99mTc by sterilely adding 99mTc-pertechnetate, obtained from readily available generators in nuclear medicine labs. After 10 minutes at room temperature a rapid quality control test is done to confirm complete binding of the 99mTc and the agent is ready to be administered to the patient.
The putative structure for 99mTc-Glucarate is shown in the figure. D-Glucaric acid, an endogenous end-metabolite derived form UDP-glucose normally not reutilized as a metabolic substrate, competes with fructose and partly with glucose for active uptake by cells with enhanced metabolic needs. Technetium-99m is inexpensive and widely available through a generator system. The radionuclide has a short 6-hour half-life and an optimal energy for efficient gamma camera detection.
Pharmacokinetic and biodistribution data in animals have shown that the kidney is the principle route of elimination of glucarate-derived radioactivity. The recommended human dose of 99mTc-Glucarate is 12.5 mg.
99mTc-Glucarate is used in the field of Nuclear Medicine. The strength of Nuclear Medicine is that it provides diagnostic information of function and physiology rather than just anatomy. Nuclear medicine studies are performed by intravenously injecting a radionuclide labeled agent which then localizes in the targeted organ or tissue within the body. An instrument called a Gamma Camera detects the emissions from the agent’s radiolabel and generates an image showing the location of the agent. The images generated by this system can be acquired and displayed on film or on a computer screen in a two dimensional or planar image. In an imaging technique called SPECT (Single Photon Emission Computed Tomography) the radiation is measured 360 or 180 degrees around the body circumference and the image can be displayed in a three-dimensional mode on a computer screen. The imaging mode employed depends upon the type of information required by the physician.
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