Nuclear Medicine uses radioactive isotopes and labeled compounds to:
the different organs in the body based on normal organ function
disease based on metabolic deviations from normal.
the nature of the abnormality by identifying specific metabolic defects.
changes based on temporal changes and response to stress, and
using much higher doses of drugs targeted to the specific tumor.
Roentgen’s discovery of X-rays in 1895 was followed a year later by Becquerel’s discovery of natural radiation emitting substances. Biological applications advanced rapidly as physicists tested the new radiations on themselves, their associates, and shortly on patients. A highlight of the rapid progress follows: In 1899, Rutherford discovered alpha and Beta radiations. In the next year he discovered the phenomena of half-life, and half-thickness regarding radiation path length. The Curie’s discovery and separation of Radium in 1903 led to a cancer therapy trial and early detrimental effects informed awareness of the balance between adverse and beneficial effects of ionizing radiations. In 1904 Thompson and Nagaoka independently proposed a model on the structure of the atom. In 1911, Rutherford proposed his theory of nuclear structure. In 1913, Niels Bohr proposed a more expanded model of the atom.
Emerging knowledge of atomic, and nuclear physics ended centuries of speculation on the fundamental state of nature. New knowledge based on measurements of the properties of the atom and the discovery of fundamental particles quickly followed. The discovery of radioactive elements led almost immediately to medical testing , as it had following the first discovery of X-rays. The first l use of tracers in was demonstrated in 1923/24 by Hevesy used naturally occurring radioactive materials to track mechanisms in plants. In Boston in 1928, Blumgart, Yens and Weiss made the first human tracer measurements of the central circulation time in normal and diseased patients. They did this by IV injections of 222Rn (radon) gas in solution, to measure the time it took it for the dissolved gas to flow through the lungs to the opposite arm as a measure of the transit time.
In 1930, Ernest Lawrence invented the Cyclotron that accelerated increasingly energetic charged particles. With this development, the Berkeley scientists discovered and produced useful amounts of a number of previously unknown radioactive elements. They used these to explore and demonstrate the characteristics of the newly discovered radionuclides in many basic and applied studies. The physics and chemistry faculty and staff, along with Ernest’s physician brother, John, developed and tested their use in many biological, chemical and medical applications, while gaining new processing methods. In 1932 Chadwick discovered the neutron, and Anderson discovered the positron. In 1934, the neutron was discovered, and shortly thereafter used by Fermi to produce 128I. Ernest Lawrence’s initial vision for Berkeley cyclotron applications in 1930 had been to gain new knowledge on the state of nature (matter) by studying changes in the elements in elemental targets, and in the particles emitted following bombardment with increasing energies of protons, deuterons, and alpha particles.
Radionuclide Research Discoveries
After Joliot and Curie discovered artificial radioactivity in 1933, direction of the cyclotron activities were diverted to the study of the potential uses of the new tracers they were able to produce. Fermi produced 128I by neutron bombardment of 127I in 1934. In Berkeley, 15O was discovered by McMillan and Livingston at in 1935. 59Fe was first produced in 1935/6 by Kamen who used it at Berkeley and shared it with colleagues at the University of Rochester. Hahn and Whipple at Rochester used Berkeley’s first shipments of 59Fe in studies of iron deficiency anemia in dogs and later in people. In Copenhagen, Bohr’s lab produced small amounts of 32P and 24Na for use by Hevesy, to supplement material they received from Berkeley. Hevesy administered 32P labeled phosphate to rats to study bone turnover. 11C was first produced in Berkeley 1936 by Kamen and Ruben where it was used in biological studies. With an interest in therapy, John Lawrence used 32P in treatment of a leukemia patient. Hamilton and Stone studied the dynamics of 24Na turnover in a leukemia patient. In 1938, Seaborg and Livingston discovered 131I and 60 Co and Seaborg and Segre discovered 99mTc. In 1940, Kamen and Ruben discovered 14C which greatly accelerated their work on carbohydrate chemistry due to its long half-life than 11C. In 1946, 125I was discovered by Reid and Keston. These pioneering biomedical advances were made in Berkeley by faculty and students that had direct access to materials from Lawrence’s cyclotrons.
Much of the early work on iodine metabolism was done in animals by the Berkeley group (Hamilton and Soley) and by Hertz and Roberts in Boston and MGH/MIT collaborations. Many of the early studies in patients were done by the Boston group, led by Hertz (Director of the Thyroid clinic at the Massachusetts General Hospital (MHG), and later by Chapman who succeeded him at MGH. The Berkeley and Boston groups did the earliest animal studies of thyroid kinetics and mechanisms that led to the many modern diagnostic and therapeutic uses of radioactive iodines. Initial studies were limited by the short half-life of 128I, and 130I, but the subsequent discovery of 131I by Livingood and Seaborg at Berkeley, produced the agent that has had the greatest value in thyroid diagnosis and therapy, along with its many other imaging and therapeutic uses. Radioiodine was used in many institutions in the United States, Europe and Asia with increasing frequency after 1945. This was spurred by the increased availability of low cost, pure 131I as WWII reactor production came on line and the material was distributed widely to research and development centers.