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| Fig. 1: Radioactive Decay of Tc-99m, Mo-99, and Ra-233 as given by Eq. (1) with t1/2 = 6 hours, 66 hours, and 11.4 days, respectively. (Image Source: D. LaJoie) |
Having been around since 1936, when John Lawrence pioneered the P-32 radioactive isotope to be used for treatment on a leukemia patient, nuclear medicine has become very prominent in todays medical diagnostics and therapeutics, offering unparalleled insights into the physiology and pathology of the human body. [1] Of the roughly 40 million nuclear medicine procedures performed each year, an astounding 13.5 million (34%) are conducted in the United States. [2] Of the procedures conducted in the United States, SPECT scans in the cardiology department was responsible for approximately 50% of them, while PET scans, primarily conducted in the Oncology department, roughly captured a 14% share. [3] Also of note, Tc-99m, an isotope of the artificially produced element Technetium, is the most commonly used radioisotope in nuclear medicine and is employed in roughly 80% of all nuclear medicine procedures. [4]
Comprised of a myriad of different forms, nuclear medicine is a medical specialty that utilizes radioactive tracers, also known as radiopharmaceuticals, to assess bodily functions and to diagnose, stage, and treat diseases. The tracers are composed of carrier molecules that are bonded tightly to a radioactive atom and are introduced into the body via injection, swallowing, or inhalation. [5] Depending on the method of screening and body part to be examined, the radionuclides and carrier molecules may vary significantly. Many tracers employ molecules that interact with a specific protein or sugar in the body, sometimes even utilizing the patient's own cells as carrier molecules. [6] Specially designed cameras then allow physicians to track the path of these radioactive tracers via unique scans, which then enables them to get a better understanding of what is happening inside the body. Two of the most commonly employed imaging modalities in nuclear medicine are single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) scans. PET exploits the unique decay physics of positron-emitting radionuclides to produce 3D images and is chiefly employed to detect cancer and monitor its progression and response to treatment. [5] SPECT uses gamma-emitting radionuclides, most commonly Tc-99m, to obtain 3D images and is used extensively to study cardiac health and blood flow to the brain. [4] As for radionuclide therapy and treatment purposes, the radioactive tracers may be used to target tumor sites and deposits lethal doses of radiation in an attempt to destroy or inhibit the growth of cancer cells. [5]
One factor that must be taken into account with nuclear medicine is the half-life t1/2 of radioisotopes. The half-life characterizes the probabilistic decay law
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(1) |
As shown in Fig. 1. this varies from one product to another. The half-life, also referred to as shelf life, of radioisotopes is notably short. Failure to use radioisotopes within their allotted timeframe will result in chemical degradation. This compromises the purity of the radionucleotides so much that employing these substances in patients for therapeutic or diagnostic purposes could prove to be deadly. [7] Because of the varying half-lives, depending on the body tissue being examined and the tracer being used, some scans are completed in minutes, while others may require the patient to return a few times over the course of several days. [8]
Another factor that must be accounted for with nuclear medicine is radiation exposure. The effective dose is a calculated dosage based on the type of radiation and the detriment to tissues exposed and varies with different types of procedures. In contrast to the sixfold rise in medical radiation exposure that occurred from 1980 to 2006 in the United States, the annual average individual effective dose decreased approximately 27% from 3.0 to 2.2 millisieverts (mSv) in the U.S. from 2006 to 2016. The collective effective dose, or the number of procedures multiplied by the effective dose per procedure, was 717,000 person-Sv in the United States (17.6% of the world's total) in 2016. Lastly, the average individual effective dose, can be defined as the collective effective dose divided by the total population, regardless of whether the persons were exposed or not. Examining further, the collective effective dose and the average individual effective dose in the in 2016 in the U.S. resulting solely from nuclear medicine was found to be 133,000 person-Sv (18.5% of U.S. total), and 0.41 mSv (18.6% of U.S. total), respectively. [2] Analyzing treatment-specific radiological exposure levels, studies found the average patient radiation exposure of PET and SPECT scans to be approximately 1.1 × 10-3 mSv and 9.0 × 10-3 mSv per MBq (106 Bq) of radioactivity from the administered radioisotopes, Rb-82 and Tc-99m, respectively. [9] However, with cancer treatment, the targeted tumor receives a much higher average dose of 30-40 Gy (30,000-50,000 mSv) per treatment. [10] The amount of radioactivity associated with this average dosage varies with tumor size, location, and the isotope used. One study in particular, which successfully utilized Radium-223 therapy for prostate carcinoma, employed a constant activity of 50 kBq/kg, which was administered every four weeks for a total of six cycles. [11] As for the radiation exposed to medical staff, the average dose received by the technician for a single treatment is approximately 10 nSv/MBq and 13 μSv/GBq of the administered radioactivity for PET and SPECT procedures, respectively. [12]
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| Fig. 2: Mo-99/Tc-99m Supply Chain. (Image Source: D. LaJoie, after the NEA. [12]) |
The previously mentioned and most commonly used radioisotope in nuclear medicine, Tc-99m, is obtained from the radioactive decay of its parent isotope, Molybdenum-99 (Mo-99). Because Mo-99 and Tc-99m have half-lives of 66 hours and 6 hours, respectively, (see Fig. 1) neither of these products can be stored for long periods of time. Therefore, supply is a time-dependent activity that requires sufficient capacity for ongoing production and a reserve in case of unplanned outages, which is modeled by Fig. 2. Nuclear research reactors (NRRs) perform the primary irradiation services and are sourced from a select few research reactors, with the majority coming from the Netherlands, Australia, Belgium, and South Africa. The bulk supply of irradiated Mo-99 is then transported in special shipment containers to processing facilities before then being sent to generator manufacturers. Because the quantity of material shipped reduces by approximately 1% per hour, the timing of these shipments is critical, and any delay will result in lost money and a possible supply shortage. The generator manufacturers then deliver the generators, which are specialized containers of Mo-99, to nuclear pharmacies, where they then elute Tc-99m to prepare patient doses. For reference, Cardinal Health, the largest nuclear pharmacy chain in the United States, supplies around 50% of all demand in the United States and consumes more than 20% of all Mo-99 produced worldwide. [13]
Henceforth, nuclear medicine in the United States represents a vital and highly advanced sector of medical diagnostics and therapeutics. Although radiological exposure and the management of radioactive decay present challenging issues, the U.S. stands at the forefront of both the consumption and implementation of nuclear medicine. The intricate and time-dependent supply chain of radioisotopes, mainly Mo-99 and its conversion to Tc-99m, highlights the complexity and efficiency of this sector.
© Dominic LaJoie. The author warrants that the work is the author's own and that Stanford University provided no input other than typesetting and referencing guidelines. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.
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