Harwood Nuclear Chem

By 1961, two more countries had developed and successfully tested nuclear weapons. United Kingdom had started its program during the Second World War in close co-operation with the United States, and the first British bomb was tested on October 3, 1952. On February 13, 1960, France followed suit. The French program received very little technological and scientific support from other countries. Four and a half years later, on October 16, 1964, China became the fifth nuclear power after having received only reluctant assistance from the Soviet Union.

In the early 1960s, many military experts and political leaders feared that the proliferation of nuclear weapons was bound to continue, and that within a decade or two a dozen additional countries were likely to cross the nuclear threshold. In an attempt to forestall such a development, the United States and the Soviet Union took the lead in negotiating an international agreement that would prohibit the further spread of nuclear weapons without banning the utilization of nuclear energy for peaceful purposes. The result was the Treaty on the Non-Proliferation of Nuclear Weapons, also referred to as the Non-Proliferation Treaty, or NPT, which opened for signature on July 1, 1968. By then, 21 countries in Latin America and the Caribbean had already established the world's first nuclear weapons-free zone by signing on to the Treaty of Tlatelolco.

When it came into force on March 5, 1970, the NPT separated between two categories of states: On the one hand, nuclear weapons states – that is, the five countries that were known to possess nuclear weapons at the time when the Treaty was signed (United States, Soviet Union, United Kingdom, France and China). On the other hand, non-nuclear weapons states – that is, all other signatories of the Treaty. According to its provisions, the nuclear weapons states on signing the NPT agree not to release nuclear weapons or in any other way help other states to acquire or build nuclear weapons. At the same time, the non-nuclear weapons states signatories agree not to acquire or develop "nuclear weapons or other nuclear explosive devices." In exchange for this self-denial, the nuclear weapons states promise to move toward a gradual reduction of their arsenals of nuclear weapons with the ultimate goal of complete nuclear disarmament.

The NPT was first signed by the United States, the United Kingdom, the Soviet Union together with 59 other countries. China and France acceded to the Treaty in 1992. In 1996, Ukraine, Belarus and Kazakhstan gave up their nuclear weapons, left over from the Soviet Union when it fell apart in 1991-92, and signed the NPT as non-nuclear weapons states parties. The NPT is now the most widely accepted arms control agreement. As of June 2003, all members of the United Nations except Israel, India, and Pakistan had signed the NPT. However, one signatory, North Korea, had recently threatened to withdraw from the Treaty.

As mentioned, the NPT distinguished between nuclear weapons states and non-nuclear weapons states as parties of the Treaty. However, from the very beginning there was in fact a third category of countries as well, namely, non-nuclear weapons states that for one reason or another had decided not to become parties of the NPT. Some countries, like Cuba, dismissed the NPT as an instrument that served to maintain the existing and, in their opinion, thoroughly unjust world order. Others simply wanted to reserve the option of developing their own nuclear arsenal: either to enhance their regional or international status, to deter military aggression or to underpin their political independence. Not surprisingly, most of the threshold states belonged to this group.

The first country outside the NPT to cross the nuclear threshold was India, which exploded a nuclear device in an atmospheric test in 1974. In 1998, both India and Pakistan conducted several nuclear underground tests, inviting a storm of international protests and some short-lived economic and political sanctions as well.

Meanwhile, the ending of white minority rule in South Africa in 1993 had led to the sensational disclosure that, in the mid-1980s, South Africa had developed and stockpiled a small number of nuclear weapons. The weapons had been dismantled and destroyed in the last years of apartheid because the white government feared that they might some day fall into the hands of militant black opposition groups and be used against the government. Subsequently, South Africa signed both the NPT (1991) and the CTBT (1996) as a non-nuclear weapons state.

Nuclear power plants generate electricity by heating fluid via a nuclear reaction to run a generator. If the heat from that reaction is not removed adequately, the fuel assemblies in a reactor core can melt. A core damage incident can occur even after a reactor is shut down because the fuel continues to produce decay heat. A core damage accident is caused by the loss of sufficient cooling for the nuclear fuel within the reactor core. The reason may be one of several factors, including a loss-of-pressure-control accident, a loss-of-coolant accident (LOCA), an uncontrolled power excursion or, in reactors without a pressure vessel, a fire within the reactor core. Failures in control systems may cause a series of events resulting in loss of cooling. Contemporary safety principles of defense in depth ensure that multiple layers of safety systems are always present to make such accidents unlikely.

The containment building is the last of several safeguards that prevent the release of radioactivity to the environment. Many commercial reactors are contained within a 1.2-to-2.4-metre (3.9 to 7.9 ft) thick pre-stressed, steel-reinforced, air-tight concrete structure that can withstand hurricane-force winds and severe earthquakes.

A core melt accident occurs when the heat generated by a nuclear reactor exceeds the heat removed by the cooling systems to the point where at least one nuclear fuel element exceeds its melting point. This differs from a fuel element failure, which is not caused by high temperatures. A meltdown may be caused by a loss of coolant, loss of coolant pressure, or low coolant flow rate or be the result of a criticality excursion in which the reactor is operated at a power level that exceeds its design limits. Alternately, in a reactor plant such as the RBMK-1000, an external fire may endanger the core, leading to a meltdown. Once the fuel elements of a reactor begin to melt, the fuel cladding has been breached, and the nuclear fuel (such as uranium, plutonium, or thorium) and fission products (such as cesium-137, krypton-85, or iodine-131) within the fuel elements can leach out into the coolant. Subsequent failures can permit these radioisotopes to breach further layers of containment. Superheated steam and hot metal inside the core can lead to fuel-coolant interactions, hydrogen explosions, or water hammer, any of which could destroy parts of the containment. A meltdown is considered very serious because of the potential for radioactive materials to breach all containment and escape (or be released) into the environment, resulting in radioactive contamination and fallout, and potentially leading to radiation poisoning of people and animals nearby.

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.