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| Fig. 1: A microscope image of a thyroid tumor cell attached to gold surface. (Source: Wikimedia Commons) |
A major reason for the public's mistrust of nuclear energy are the major health risks associated with exposure to radioactive material, ranging from increased risk of cancer to death. Interestingly, while radioactive particles may cause certain health problems, they are also able to help treat others. Targeted radiotherapy involves the selective introduction of radioactive particles to cancerous tissue, where the radiation poisons the cancerous cells with minimal effects on normal ones. Currently, radiotherapy is one of the most effective forms of cancer treatments, with around 50% of cancer patients receiving it in some form. [1] A subset of this type of treatment is known as nuclear medicine therapy, which involves direct insertion of unsealed radioactive molecules into the body, as opposed to using an external beam or radioactive sources within a container. This report is focused on nuclear medicine therapy's evolution, obstacles and prospects.
Radionuclide treatment began when early radiologists touted radioactivity to be "God's given gift" following the isolation of Radium by the Curies, and believed it to have natural energizing properties. Early "treatment" included injections, tonics, bath salts and ointments containing radium. Despite lack of clinical evidence, these therapies supposedly improved a variety of conditions such as "arthritis, gout, neuralgia, lumbago, menstrual irregularities, sexual disorders and obesity." Clinical treatments did not progress until the 1930s, when we learned to artificially produce radioactivity. The first clinical radionuclide treatments used isotopes of phosphorus and iodine to treat thyroid cancer, laying the foundations for nuclear medicine therapy today. [2]
We begin with a deeper look at how nuclear medicine therapy works. Radioactive particles are attached to certain molecules that get selectively collected by the target cells. These carrier molecules take the radioactive particles to the selected sites, bypassing normal cells. One important aspect of this treatment is that it needs not be incorporated into every single target cell. Instead, by varying the radioactivity of the particle, one can control the area of effect of the treatment, making it possible to affect a target area while limiting the spread from affecting normal cells. The the most well-established uses of nuclear medicine therapy today are:
Thyroid Cancer: Thyroid cancer accounts for nearly 2% of all new cancers diagnosed annually in the US. An example of a thyroid tumor cell is shown in fig. 1. The most common types (papillary and follicular) have relatively favorable prognosis, with 10-year survival rates ranging from 80-95%. The survival rates drop for the less common types, with medullary thyroid carcinoma at 65%-80% and a 50% 5-year survival rate in primary thyroid lymphoma. Surgery remains the treatment of choice for this type of cancer, but can be followed up with a treatment of radioiodine. [3] The iodine can be taken as solution or capsule, and is quickly absorbed from the upper gastrointestinal tract. In use for the past 50 years, its efficiency and lack of side effects make it a benchmark for new forms of nuclear medicine. [2]
Rheumatoid Arthritis:Rheumatoid arthritis is one of the most common autoimmune diseases, with approximately 1% prevalence. It causes pain, disability and immobility via the inflammation and destruction of joints. The main treatment uses various drugs to reduce the inflammation, which sufficiently suppresses the symptoms in most cases. In cases where drug treatments fail, surgery is employed to remove inflamed regions. Although this approach successfully treats the issue, prolonged rehabilitation is necessary and complications may arise, especially in hemophiliacs. [4] Nuclear medicine therapy is an alternative treatment, where either yttrium or rhenium isotopes are directly injected into the joint space, with the choice of nucleotide depending on the joint space size. Nuclear medicine therapy in this case produces results comparable to surgery, but allows the patient to remain mobile, is less expensive and avoids the complications from hemophilia. [2]
Despite steady improvement over the past few decades, progress has been slow as researchers work to find suitable conjugates that increase selectivity or apply to novel treatments. [2] The major obstacle in finding new conjugate molecules for treatments is the number of requirements such molecules have to meet. The most important one that the molecule must be able to seek out target cells with extremely high precision. Since cancerous cells originate from normal cells, it is understandably difficult to find carrier molecules that selectively bind to cancer cells and not normal cells. Additional restrictions for the carrier requires it to be safe for the patient, stable inside the body, reliable and affordable. [2] Despite these difficulties, progress is being made in both use of current carrier molecules as well as new technologies.
Improvements in biotechnology has made it possible to design, select and produce compounds capable of recognizing specific molecules. This implies a future for radiotherapy that allows researchers to design carriers that bind to the specific genetic code of different tumor-associated antigens, and sustainably produce them. Another area of research is focused on using alpha emitters, which emit a couple orders of magnitude more energy than beta particles, giving them more range and increased toxicity against selected targets. [2]
Nuclear medicine therapy is without a doubt still a growing field. After half a century since the first clinically verified uses appeared, the number of well-established treatments can still be counted on one hand. However, it has also without a doubt become a vital asset in the battle against cancer, and has become the focus of much research. Major breakthroughs in this field promises benefits to numerous types of cancer and the engineering of carrier molecules in particular hints at the "magic bullet" envisioned by Paul Ehrlich that kills only targeted organisms.
© Wayne Sheu. 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.
[1] A.C. Begg, F.A. Stewart and C. Vens, "Strategies to Improve Radiotherapy With Targeted Drugs," Nat. Rev. Cancer, 11, 239 (2011).
[2] A.C. Perkins, "In Vivo Molecular Targeted Radiotherapy," Biomed. Imag. Interv. J. 1, No. 2, e9 (2005).
[3] R. D. Blankenship, E. Chin, and D. J. Terris. "Contemporary Management of Thyroid Cancer," Am. J. Otolaryngol. 26, 249 (2005).
[4] P. Schneider, J. Farahati, and C. Reiners, "Radiosynovectomy in Rheumatology, Orthopedics, and Hemophilia," J. Nucl. Med. 46, Suppl. 1, 48S (2005).
