Wednesday, March 27, 2013

How Radioiodine Works to Cure Cats with Hyperthyroidism

Iodine Physiology and the thyroid
Thyroid hormones are the only iodinated organic compounds in the body. Ingested stable iodine (127-I) in the diet is converted to iodide in the gastrointestinal tract and absorbed into the circulation.

In the thyroid gland, iodide is concentrated or trapped by active transport mechanisms of the thyroid follicular cell, resulting in intracellular iodide concentrations that are 10 to 200 times that of the serum (Figure 1). Once inside the thyroid cell, iodide is oxidized to iodine, which is incorporated into tyrosine residues of thyroglobulin (organification) to form the thyroid hormones thyroxine (T4) and triiodothyronine (T3) (1-3).

Figure 1: Synthesis of thyroid hormones, as seen in an individual cell.
See this link for more information (2).

Radioiodine (131-I): How it works
The radioisotope used to treat hyperthyroidism is radioiodine-131 (131-I). The basic principle behind treatment of hyperthyroidism with 131-I is that thyroid cells do not differentiate between stable (nonradioactive) and radioactive iodine (3-7). Therefore radioiodine, like stable iodine, is concentrated by the thyroid gland after administration (see Figure 1).

In cats with hyperthyroidism, radioiodine is concentrated primarily in the hyperplastic or neoplastic thyroid cells, where it irradiates and destroys the hyperfunctioning tissue as the iodine is incorporated into thyroid hormone (4-7).

Unless too large of an I-131 dose is administered, normal (i.e., nonadenomatous) thyroid tissue tends to be protected from the effects of radioiodine because it becomes atrophic and takes up very little of the administered dose of radioiodine (4-7). In some cats, however, most of the normal thyroid gland has been replaced by tumor. If the I-131 treatment is successful in destroying the thyroid tumor tissue in these cats, they will likely develop hypothyroidism and will require normal thyroid hormone supplementation (4-8). I'll be discussing the issue of iatrogenic hypothyroidism more in my future posts.

Radiation physics and I-131
Radioiodine emits two types of radiation (Figure 2):
  • beta (β)-particles
  • gamma (γ)-radiation
The β-particles, which cause almost 90% of the tissue damage, travel only a very short distance —a maximum of 2 mm in tissue, with an average path length of 400 μm (3,7,9). Therefore, β-particles are locally destructive to the thyroid tumor but spare adjacent atrophic thyroid tissue, parathyroid glands, and other cervical structures.

Because they contain mass, the β-particles can be thought of as a hail of "bullets," with the cellular DNA of the thyroid tumor as the "target." The higher the I-131 exposure, the more bullets pass near or hit the target to cause the desired tumor destruction (3,7,9).

Gamma radiation, also known as gamma rays and denoted as γ, is a form of electromagnetic radiation (like X-rays). Although gamma rays are a form of ionizing radiation, this plays only a minor role in the destruction of the thyroid tumor following radioiodine treatment (3,7,9).

Figure 2: Radioiodine-131 emits 2 types of radiation — 1) gamma (γ)-radiation as a wave of electromagnetic energy, and  2) β- radiation as a particle.

Radioiodine kinetics in cats with hyperthyroidism
When radioiodine is administered to a cat with hyperthyroidism, between 20% to 60% of the administered dose is taken up and accumulates in the thyroid tumor. The remainder of the administered 131-I is excreted primarily in the urine and to a lesser degree the feces (10,11).

Radioiodine has a physical half-life of 8 days; in other words, the amount of radiation will decrease by half every 8 days (3,7,9). To reach background levels of radiation, we can calculate that I-131 will take approximately 90 days. With regard to our cats, however, we must remember that the biological or effective half-life of I-131 in the cat is much shorter than 8 days because the cats are also excreting the radioiodine into their urine and feces. Therefore, most, if not all, of the measurable radiation will be gone from our cats within 2 to 3 weeks after treatment.

  1. Miot F, Dupuy C, Dumont JE, et al. Thyroid hormone synthesis and secretion. Thyroid Disease Manager (online), 2012. 
  2. Wikipedia. Thyroid hormone
  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. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT, Peterson ME, eds. Manual of Canine and Feline Endocrinology, Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;199-203.
  6. Peterson ME. Hyperthyroidism in cats In: Rand JS, Behrend E, Gunn-Moore D, et al., eds. Clinical Endocrinology of Companion Animals. Ames, Iowa Wiley-Blackwell, 2013;295-310.
  7. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism. In: Bonagura JD, Twedt DC, eds. Current Veterinary Therapy XIIII. Philadelphia: Saunders Elsevier, 2013: in press.
  8. Nykamp SG, Dykes NL, Zarfoss MK, et al. Association of the risk of development of hypothyroidism after iodine 131 treatment with the pretreatment pattern of sodium pertechnetate Tc 99m uptake in the thyroid gland in cats with hyperthyroidism: 165 cases (1990-2002). J Am Vet Med Assoc 2005;226:1671-1675. 
  9. Ward WF. Basic principles of radiation biology. In: Henkin RE, Bova D, Dillehay GL et al. Nuclear Medicine. Elsevier, Philadelphia 2006: 507–522.
  10. Broome MR, Turrel JM, Hays MT. Predictive value of tracer studies for 131-I treatment in hyperthyroid cats. Am J Vet Res 1988;49:193-197. 
  11. Hays MT, Broome MR, Turrel JM. A multicompartmental model for iodide, thyroxine, and triiodothyronine metabolism in normal and spontaneously hyperthyroid cats. Endocrinology 1988;122:2444-2461.

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