produced isotopes (e.g., iron-59, iodine-131, and technetium-99m) that have become invaluable nuclides for nuclear molecular imaging and therapy. John H. Lawrence, a physician, used his brother Ernest’s radioisotopes in humans, treating a leukemia patient in 1937. John was also one of the early presidents of the Society of Nuclear Medicine (1966-1967). A colleague of the Lawrence brothers, Joseph G. Hamilton, coined the term “nuclear medicine” after observing John’s treatments of people with radionuclides. In the late 1930s, Hamilton asked Nobel Laureate Glenn Seaborg if he could create a radioactive isotope of iodine with a half-life of about a week for studying thyroid metabolism, and Seaborg promptly produced radioiodine (iodine-133 or 131I), which is still used for imaging and therapy of thyroid diseases.

After World War II there was enormous growth in the field of nuclear medicine. In 1946, a New York internist, Dr. Samuel M. Seidlin, together with colleagues Leo Marinelli and Eleanor Oshry at Montefiore Medical Center in New York City, treated and cured a patient with thyroid cancer using 131I obtained from Oak Ridge National Laboratory. This work was published in the Journal of the American Medical Association (Seidlin et al. 1946) and produced a flurry of publicity. After this, there were almost yearly discoveries in the new field of nuclear medicine, in both chemistry and physics. The development of instruments to detect the various decays of radionuclides went hand in hand with new discoveries in radiopharmaceuticals.

No one could have predicted how valuable the cyclotron would become to modern molecular imaging for the production of a variety of radionuclides, especially the short-lived positron-emitting isotopes of carbon, nitrogen, oxygen, and fluorine. The availability of both small academic- and hospital-based cyclotrons spurred growth of the field and now regional cyclotron facilities have increased the availability of PET tracers, mostly through the production and distribution of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]fluorodeoxyglucose, FDG), the most widely produced and indispensable molecular imaging agent. Figure 4-1A shows the international growth in publications about FDG since 1990. Figures 4-1B and 4-1C show the growth in publications for newer areas of nuclear medicine involving Fluorine-18 and Gallium-68. While the growth for both of these new areas is dominated by German- and U.S.-authored papers, more recently many other countries mostly in Europe and Asia are now contributing to the steep growth in numbers of publications in these areas.

RADIONUCLIDE PRODUCTION

There are three major sources for the production of radionuclides for nuclear medicine applications—particle accelerators (linear and cyclotrons),



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