Dr Hans Biersack has put together a stellar group of investigators in this issue to review some of the important therapeutic radionuclide applications and to present some exciting recent developments.
The use of labeled peptides and MIBG for therapy have not received Food and Drug Administration (FDA) approval for use in the United States at this time. The success of these treatments shown by our European colleagues in this seminar may help to achieve FDA approval in the not too distant future.
Treatment of well differentiated thyroid cancer is one of the earliest procedures in nuclear medicine. Interestingly, a Montefiore endocrinologist, Dr Sam Seidlin, published his seminal paper on radioiodine therapy in the December 7, 1946 issue of the Journal of the American Medical Association. This prophetic date was not only the five year anniversary of Pearl Harbor Day, but was also 16 months after atomic bombs were dropped on Hiroshima and Nagasaki. The level of apprehension from this latter event can be best appreciated by speaking to anyone who recalls his or her emotions following the more recent events of September 11, 2001. During the year following the end of World War II, the US Congress debated how to regulate nuclear energy and the frightening potential sequelae of its use in war. Seidlin's paper appeared in the midst of this debate. For the first time, it was shown dramatically that nuclear energy could be used effectively for peaceful purposes, such as treating thyroid cancer. This laid the groundwork for all of the support and research funding nuclear medicine received during the ensuing half century. One of our well known pioneers, Dr Marshall Brucer, referred to Seidlin's paper as the single most important article ever written in nuclear medicine, since there might not have been any nuclear medicine without it or any the subsequent government support it engendered.
Although iodine-131 is a plentiful reactor product, the US has failed to keep up with the widening use of radioactive materials in medicine that has followed Dr Seidlin's original article and gone beyond radioiodine. Consequently, at this time, there is a shortage of the material that has become our most important radionuclide, technetium-99m (99mTc). Its parent compound, molybdenum-99 (99Mo) is produced in nuclear reactors that utilize highly enriched uranium-235 (HEV) targets.
The only reactor in North America (located in Chalk River, Canada) was closed suddenly in the Spring of 2009 for needed repair. This created an immediate crisis situation necessitating increased reliance on four other reactors located in the Netherlands, Belgium, France, and South Africa.
The raw 99Mo from the reactors is purchased by two major US companies, Covidien and Lantheus, who manufacture the generators distributed to local nuclear medicine pharmacies. Despite efforts to compensate for the Chalk River closing by enhancing supply from the European reactors, a significant shortage of 99mTc has occurred. This has seriously curtailed the performance of many of our every day procedures, such as bone scintigraphy. All of us have had to deal with patient scheduling changes, as well as adjustments in calibration times and delivery schedules. This has had an enormous impact on our ability to provide optimal patient care.
Alternatives have been suggested, particularly in relation to the frequently performed bone scan. A viable alternative to 99mTc-methylene diphosphonate is the positron agent, 18F-sodium fluoride. This material is FDA approved, but has received limited approval for reimbursement by the Centers for Medicare and Medicaid Services (CMS). This approval is limited to identifying metastases to assist initial treatment strategy or to guide subsequent treatment strategy after completion of initial therapy in patients with cancer. Although it represents some progress, it still falls short of covering the many other clinically proven applications of bone scintigraphy in the realm of benign disorders, such as infection and trauma. 18F-fluoride is a cortical imaging agent whose localization in bone is similar to that of the phosphate compounds. Direct comparisons between the two agents suggest that the positron agent may be superior.1 It is certainly hoped that CMS will broaden its coverage to help alleviate the problems in bone scanning caused by the technetium shortage.
In another recent development, the US Congress finally has recognized the need to have a domestic production source available so as not to depend solely on foreign reactors for our supply of 99mTc. The American Medical Isotopes Production Act of 2009 (H.R. 3276) was passed on November 5, 2009.2 It recognizes that “there is a critical shortage of molybdenum-99 to satisfy domestic medical isotope needs.” It amends the longstanding Atomic Energy Act of 1954 to authorize the Nuclear Regulatory Commission to issue a license or amend an existing license that will allow the creation of reactors using highly enriched uranium for use as a target for the production of medical isotopes. We applaud this long overdue legislation that finally will allow us to be self sufficient in having 99Mo and its daughter product, 99mTc, available to optimize patient care.
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