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The potential use of radioiodinated fatty acids as myocardial imaging agents Chung, Connie Joan

Abstract

The potential use of four radioiodinated fatty acids as myocardial imaging agents were evaluated. Preliminary distribution studies revealed that the terminal labeled fatty acids demonstrated higher myocardial uptake. Thus, 10-Iodocapric acid (10-iododecanoic) and 12-Iodolauric acid were subjected to further investigation. Comprehensive tissue distribution studies involving both radioiodinated fatty acids in mice indicated that the highest accumulation of the total injected activity occurred in the muscle and the blood. Other organs investigated included the heart, liver, lung, kidneys, spleen, stomach, intestines, bone and adrenals. The heart exhibited the highest concentration of the radioiodinated fatty acids for the relative accumulation of activity per unit weight. Erom the tissue distribution studies, the optimum scanning time was found to be immediately following injection of the radiopharmaceutical. Toxicity studies were performed in mice after intravenous administration of 10-Bromocapric acid and 12-Bromolauric acid. The LD₅₀ of Sodium Bromolaurate in 10% Human Serum Albumin was found to be 210 mg/kg (194 mg/kg - 228 mg/kg). The stability problem encountered with 10-Bromocapric acid necessitated the use of a different solvent system. The LD₅₀ obtained after intravenous injection was found to be 86.1 mg/kg (83.0 mg/kg - 89.3 mg/kg). However, this observed toxicity may not necessarily reflect the toxicity of the Bromocapric acid solely. Whole body excretion studies were performed in mice and revealed a triexponential excretion curve. For 10-Iodocapric acid, the effective half-lives were .90 hours (36.7%), 3.91 hours (61.6%) and 74.9 hours (14.5%). For 12-Iodolauric acid, the effective half-lives were 1.67 hours (46.6%), 7.68 hours (38.4%), and 71.6 hours (17.8%). For both 10-Iodocapric acid and 12-Iodolauric acid, the first as well as the second component of the excretion curve presumably represented a decrease in the whole body activity due mainly to urinary excretion. The third component appeared to represent activity which was tightly bound and slowly released. The third component presumably represented elimination by fecal excretion. The excretion of the injected activity was primarily in the urine, although some activity was recovered in the feces. For 10-Iodocapric acid, 82.4% of the injected activity had been recovered in the urine within the first 24 hours and 8.88% had been recovered in the feces. For 12-Iodolauric acid, 78.9% of the injected dose was recovered in the urine at 24 hours and 9.4% in the feces. From the urine results, the effective half-life of the radio-iodinated fatty acids in the kidneys was found to be 4.8 hours. Myocardial scans were done on rabbits using ¹³¹I-capric acid, ¹³¹I-lauric acid, NaI-131 (6% Human Serum Albumin), and Thallium-201 at specified time intervals after injection. Iodine-123, a radionuclide possessing more favorable imaging properties, was not readily available due to production problems at the time of scanning. The mean absorbed dose to the whole body, the liver, the kidneys, the muscle, and the heart were computed based on the results from the distribution and excretion studies. The dosimetry calculations were done using Iodine-123 as the radionuclide. For ¹³¹I-capric acid, the radiation doses were calculated as 34.76 mrads/2 mCi for the whole body, 136.3 mrads/2 mCi for the kidneys, 86.6 mrads/2 mCi for the liver, 38.5 mrads/2 mCi for the muscle, and 25.89 mrads/2 mCi for the heart. For ¹³¹I-lauric acid, the radiation doses were 41.73 mrads/2 mCi for the whole body, 199.8 mrads/2 mCi for the kidneys, 185.9 mrads/2 mCi for the liver, 52.07 mrads/2 mCi for the muscle, and 46.39 mrads/2 mCi for the heart.

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