The Many Isotopes of Radioiodine and Their Uses in Medicine

My question is about using radioactive iodine (radioiodine) to treat hyperthyroidism. Is radioiodine-131 (131-I) the only radioisotope we can use to treat this condition? Have you (or anyone else) ever used other radioisotopes of iodine for treatment of hyperthyroidism, such as 123-I, 124-I, or 128-I?

If I-131 is the only form of radioiodine used to treat hyperthyroidism, do the other isotopes of radioiodine have any other medical uses for imaging or therapy?

My Response:

There are 37 known isotopes of iodine (I) from 108-I to 144-I, but only one, 127-I, is stable (i.e., nonradioactive). So as you stated, there are a number of forms of radioiodine other than 131-I (1,2).

Of all of these iodine radioisotopes, only 4 are used as tracers or therapeutic agents in medicine. These are 123-I, 124-I, 125-I, and 131-I. Essentially all industrial production of radioiodine isotopes involves these 4 useful radionuclides.

Of these, however, only I-131 is useful for treating hyperthyroidism. To understand why, let's review these 4 isotopes so you can understand what each of them can do for us in clinical medicine.

Iodine-131
Let's start with iodine-131 (I-131). This radioisotope of iodine has a half-life of 8 days and emits both beta-particles and gamma radiation (see Figure, above) (3-5). The beta-particles, which cause 90% of the tissue damage, are comparatively energetic, travel a maximum of 2 mm in tissue, and have an average path length of 400 μm. Therefore beta-particles are locally destructive to the thyroid tumor but spare adjacent atrophic thyroid tissue, parathyroid glands, and other cervical structures (3-5).

When very high doses are administered, it can also be useful to treat thyroid carcinoma in cats (5-7). In dogs, I-131 is less commonly used, but will work to destroy the thyroid tumor if it is functional and will take up enough I-131 to destroy the tumor (6,8).

I-131 also emits gamma radiation (about 10% of its energy), but this does little actual tissue damage. However, because of this emitted gamma radiation, I-131 can be "seen" by nuclear medicine imaging techniques (i.e., gamma cameras) (2,9). I-131 is almost never used for thyroid scintigraphy, however, since other less-damaging radioisotopes of iodine (I-123, see below) or technetium-99m are preferred in diagnostic situations when only nuclear imaging is required (9).

Figure 1— Decay of radioiodine-131 (I-131)  As I-131 decays (half-life of 8.0 days), it emits both beta-particles and gamma ray energy. The primary emissions of 131-I decay are electron (beta) particles, which are responsible for 90% of the thyroid tumor destruction. Most other radioisotopes of iodine are primarily gamma-emitters (no beta-particle emission).
Iodine-123
Radioiodine-123 is primarily a gamma-emitter with a relatively short half life (13 hours). The main use for I-123 is as a nuclear imaging tracer (i.e., thyroid scintigraphy) to evaluate the anatomic and physiologic function of the thyroid (2,9,10).

I-123 decays by electron capture (EC) to emit a high-speed internal conversion electron (not a beta ray), but this does little cellular damage due to the nuclide's short half-life and the relatively small fraction of such events. In addition, I-123 decays to emit a 159 keV gamma ray, which is well-suited for nuclear imaging (nuclear scintigraphy).

Most authorities consider I-123 to be the radionuclide of choice for imaging the thyroid gland (9,10). However, I-123 is worthless for treating hyperthyroidism because this gamma radiation doesn't help us in destroying thyroid tissue (we need the beta particles emitted by I-131 to do this).

Iodine-125
Iodine-125 (125-I) is a radioisotope of iodine which has uses in biological assays (e.g., radioimmunoassays) and in radiation therapy as brachytherapy (i.e., to treat prostate cancer and brain tumors). It also has a more limited role in nuclear medicine imaging.

Because of its relatively long half-life (59 days) and emission of low-energy photons which can be detected by gamma-counter crystal detectors, I-125 is a preferred isotope for tagging antibodies in radioimmunoassay and other gamma-counting procedures involving proteins outside the body (11). These same properties of the isotope make it useful for brachytherapy and for certain nuclear medicine scanning procedures, in which it is attached to proteins (albumin or fibrinogen), and where a longer half-life than provided by I-123 is required for tests lasting several days.

In addition to its use in biological assays, iodine-125 is also commonly used by radiation oncologists as brachytherapy to treat cancer at sites other than the thyroid, especially in human prostate cancer (12,13). When I-125 is used therapeutically, it is encapsulated in titanium seeds and implanted in the area of the tumor, where it remains. The low energy of the gamma spectrum in this case limits radiation damage to tissues far from the implanted capsule.

Again, I-125 is used therapeutically (to destroy tumor tissue) only in brachytherapy. Because this radioisotope does not emit any beta particles, I-125 is not effective for treatment of hyperthyroidism or ablation of thyroid carcinoma (3).

Iodine-125 has been used for thyroid imaging, but iodine-123 is preferred for this purpose, due to its better radiation penetration and shorter half-life (13 hours vs. 59 days) (10).

Iodine-124
Iodine-124 is a proton-rich isotope of iodine with a half-life of 4.18 days. Its modes of decay are about 75% electron capture and 25% positron emission. Like iodine-123 and I-125, this isotope emits no beta radiation and cannot be used for treatment of hyperthyroidism.

The main use of iodine-124 is to directly image the thyroid using positron emission tomography (PET scanning) (). Iodine-124 can also be used as a PET radiotracer with a usefully longer half-life compared with fluorine-18. In this use, the nuclide is chemically bonded to a pharmaceutical to form a positron-emitting radiopharmaceutical, and injected into the body, where again it is imaged by PET scan (14-16).

References:
  1. Johnson PM, Sciarra JJ, Stickley EE. Radioactive iodine isotopes. Rev Argent Endocrinol Metab 1964;10:93-94. 
  2. Croft BY, Tsui BMW. Nuclear medicine. In: Medical Imaging: Principles and Practices. Analoui M, Bronzino JD, Peterson DR (eds). Boca Roton, FL: CRC Press, Taylor & Francis Group. 2013:4-1.
  3. Wyszomirska A. Iodine-131 for therapy of thyroid diseases. Physical and biological basis. Nucl Med Rev Cent East Eur 2012;15:120-123. 
  4. Peterson ME. Radioiodine treatment of hyperthyroidism. Clin Tech Small Anim Pract 2006;21:34-39. 
  5. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2013;in press.
  6. Feeney DA, Anderson KL. Nuclear imaging and radiation therapy in canine and feline thyroid disease. Vet Clin North Am Small Anim Pract 2007;37:799-821, viii. 
  7. Hibbert A, Gruffydd-Jones T, Barrett EL, et al. Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. J Feline Med Surg 2009;11:116-124. 
  8. Turrel JM, McEntee MC, Burke BP, et al. Sodium iodide I-131 treatment of dogs with nonresectable thyroid tumors: 39 cases (1990-2003). J Am Vet Med Assoc 2006;229:542-548. 
  9. Rault E, Vandenberghe S, Van Holen R, et al. Comparison of image quality of different iodine isotopes (I-123, I-124, and I-131). Cancer Biother Radiopharm 2007;22:423-430. 
  10. Park HM. 123-I: almost a designer radioiodine for thyroid scanning. J Nucl Med 2002;43:77-78. 
  11. Yalow RS. Radioimmunoassay. Annu Rev Biophys Bioeng 1980;9:327-345. 
  12. Georgakopoulos J, Zygogianni A, Papadopoulos G, et al. Permanent implantation as brachytherapy technique for prostate carcinoma-review of clinical trials and guidelines. Rev Recent Clin Trials 2012;7:173-180. 
  13. Schwarz SB, Thon N, Nikolajek K, et al. Iodine-125 brachytherapy for brain tumours--a review. Radiat Oncol 2012;7:30. 
  14. Bailey DL, Townsend DW, Valk PE, et al. Positron Emission Tomography: Basic Sciences. Secaucus, NJ: Springer-Verlag, 2005.
  15. Saha GB. Basics of PET Imaging: Physics, Chemistry, and Regulations. Second ed. New York, NY:Springer. 2010.
  16. Budinger TF VanBrocklin HF. Positron-emission tomography. In: Medical Imaging: Principles and Practices. Analoui M, Bronzino JD, Peterson DR (eds). Boca Roton, FL:CRC Press, Taylor & Francis Group. 2013;7-1.

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