Group items tagged

FDG-PETTumors and some organs, such as the brain, use glucose as a source of energy. FDG (Sidebar 2.2) is a fluorine-18-labeled derivative of glucose (fluorodeoxyglucose) which is used with positron emission tomography (PET) to provide a map of where glucose is metabolized in the body. Because tumors, as well as the brain and the heart, all use glucose as a source of energy, FDG is widely used in cancer diagnosis and in cardiology, neurology, and psychiatry. FDG is now widely available to hospitals throughout the United States and the world from a network of regional commercial cyclotron/FDG distribution centers (Figure 6.1). With the current large infrastructure of commercial cyclotron/FDG distribution centers, many chemists are developing other highly targeted fluorine-18-labeled compounds to take advantage of this unique network to broaden the use of PET for making health care decisions. The translation of FDG from the chemistry laboratory into a practical clinical tool had its roots in government-supported research in hot atom chemistry (see Chapter 5), cyclotron targetry, biochemistry, synthetic chemistry, nuclear chemistry, and radiochemistry that was integrated with engineering and automation (Fowler and Ido 2002).

Cancer Biology and Targeted Radionuclide Therapy.

Neuroscience, Neurology and Psychiatry

Drug Development.

Cardiovascular Disease

Genetics and Personalized Medicine.

Currently, chemists working in the areas of molecular imaging and targeted radionuclide therapy are focused on designing and synthesizing radiopharmaceuticals with the required bioavailability and specificity to act as true tracers targeting specific cellular elements (e.g., receptors, enzymes, transporters, antigens, etc.) in healthy human subjects and in patients. Goals are to make labeling chemistry occur faster, more efficiently, and at smaller and smaller scales to give labeled compounds of very high specific activity that can act as true tracers.4

specific activity is critical for imaging receptors present at a copy number of 1,000 per cell, but less of an issue with receptors such as the epidermal growth factor receptor that are present at a concentration of millions per cell.

Two high research priorities that are under investigation are carbon-11 and fluorine-18 chemistry and peptide and antibody labeling.

Of particular importance is research on the design and development of radiotracers that are more broadly applicable to common pathophysiological processes, which may be more useful and more readily commercialized (e.g., targets involved in inflammation and infection, angiogenesis, tissue hypoxia, mitochondrial targets, cell signaling targets, and targets associated with diabetes, obesity, metabolic syndrome, or liver disease).

For example, MIBG, used initially mainly for assessment of neuroendocrine tumors, is now showing promise in early diagnosis of heart failure, a major health and economic issue in the United States. It is important to keep in mind that any new developments in targeted radionuclide therapy require access to research radionuclides (see Chapters 4 and 5

Four major impediments—some of which are elaborated further in other chapters of the report—stand in the way of scientific and medical progress and the competitive edge that the United States has held for more than 50 years:

Lack of Support for Radiopharmaceutical R&D.

Shortage of Trained Chemists and Physician Scientists

Inappropriate Regulatory Requirements

Limited Radionuclide Availability

6.5. RECOMMENDATIONSThe committee formulated two recommendations to meet the future needs for radiopharmaceutical development for the diagnosis and treatment of human disease and to overcome national impediments to their entry into the practice of health care. RECOMMENDATION 1 : Enhance the federal commitment to nuclear medicine research. Given the somewhat different orientations of the DOE and the National Institutes of Health (NIH) toward nuclear medicine research, the two agencies should find some cooperative mechanism to support radionuclide production and distribution; basic research in radio nuclide production, nuclear imaging, radiopharmaceutical/radiotracer and therapy development; and the transfer of these technologies into routine clinical use. Implementation Action 1A1: A national nuclear medicine research program should be coordinated by the DOE and NIH, with the former emphasizing the general development of technology and the latter disease-specific applications. Implementation Action 1A2: In developing their strategic plan, the agencies should avail themselves of advice from a broad range of authorities in academia, national laboratories and industry; these authorities should include experts in physics, engineering, chemistry, radiopharmaceutical science, commercial development, regulatory affairs, clinical trials, and radiation biology. RECOMMENDATION 2: Encourage interdisciplinary collaboration. DOE-OBER should support collaborations between basic chemistry and physics laboratories, as well as multi-disciplinary centers focused on nuclear medicine technology development and application, to stimulate the flow of new ideas for the development of next-generation radiopharmaceuticals and imaging instrumentation.