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.

One frequently expressed concern is that Iran would consider its nuclear weapons capability to be held in trust for the Islamic world or would give custody of a weapon to someone else, perhaps even a terrorist group. Such an outcome is theoretically possible, but not very probable. With one notable and quickly regretted exception—Soviet transfer of some U-235 to China in the 1950s—no country with bomb-making fissionable materials has knowingly transferred them to anyone else.

More useful to consider is the role that nuclear weapons would play in shaping post-nuclear Iran’s relationships with its neighbors—friends and foes. When all is said and done, such weapons would have little military utility except for deterrence. This would operate at four levels: to deter a conventional attack from a non-nuclear regional power; to deter an openly nuclear regional state—today only including Pakistan and India; to deter Israel; or to deter a major external power, notably the United States but, in theory at least, also including Russia.

The first case is obvious: no country with just conventional arms is likely to try the patience of a nuclear power. But in the other three cases, “proportional deterrence” would come into play. Originally developed by France, this doctrine holds that a relatively less-capable nuclear power such as Iran can deter a much stronger nuclear power (the United States, Russia, Pakistan, India, Israel) if it is viewed as able and willing to destroy “value targets” in the attacking nation even while it is being obliterated. This complex doctrine can be summarized as the “death throes” of a country under nuclear or even extreme conventional attack

Such a doctrine depends on the potential attacker such as the United States or Israel calculating that the targets in its own country that would be destroyed in retaliation would be more “valuable” to it than the benefit (military or political) of annihilating Iran. Of course, proportional deterrence can only succeed if the potential retaliation is credible, hence the need for a survivable second-strike capability. The threat of retaliation must not be so precise that the original attacking nation can calculate with precision whether the game is worth the candle (uncertainty principle). There should also be a margin for the leadership of the attacked nation to over-respond (irrationality principle). All these ideas were worked out in detail during the Cold War.

Nevertheless, as with all issues involving nuclear weapons, psychology and politics are critical elements. Indeed, if they were not—if the world had not witnessed Hiroshima and Nagasaki—we would likely have seen much more proliferation over the past 60 years, as many analysts long predicted, or even the further use of nuclear weapons in war.

As things now stand in the Middle East and are likely to stand for the foreseeable future, a nuclear-armed Iran would change the politics and the security of the region dramatically in terms of perceptions. The point need hardly be spelled out. Further, even if regional and outside countries could in time adjust to a nuclear-armed Iran, judged from today, it is highly unlikely that Iran would be permitted to gain such a capability. The United States, Israel, or perhaps some third-party would likely use whatever means necessary to prevent Iran from ever getting into that position.

noninvasive test with very low risk

electrocardiogram

(ECG), a test that detects electrical activity in the heart

different intervals in the heart’s cycle

an (MUGA) or radionuclide ventriculography (RNV).

, which shows the strength of the heart’s contraction

determine the location of a pumping problem in your heart chambers.

gain information about or diagnose other conditions.

avoid caffeine for 48 hours before the test.

The nuclear substance used during the test may be passed to the fetus or excreted in breast milk.

metal plate or screw in your body, inform your doctor and the technician.

remove all metal from your body

hospital gown so the technican has access to your ches

metal plate or screw in your body

It is normal to feel flushed or chilled as the radioactive tracer makes its way into your body

The technician will apply electrodes to different areas on your chest for the electrocardiogram.

special type of camera and begin taking pictures.

change positions in order to get certain images

exercise stress test in

heart performs during activity