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Six Tc-99m labelled dibasic acids : an investigation of their potential use as scintiscanning agents

University of British Columbia

Six low molecular weight dibasic acids labelled with technetium -99m were investigated for their potential use as scanning agents. Preliminary radioscintiscans of rabbits showed the main areas of localization for all the acids. From this study, the most promising of the compounds, malonic acid, was chosen for further investigation. Toxicity studies were performed on mice using a complex of stannous chloride and malonic acid given intravenously. The LD₅₀ for the complex was determined to be 800 (734-872) mg/kg. The excretion rate of the labelled complex was examined in mice and the activity was found to be eliminated in two components. The fast component had a half-life of 46.8 minutes, and consisted of 70.3 percent of the administered dose; the slow component, accounting for the remainder of the administered dose, had a half-life of 196.4 minutes. The excreted urine was found to contain the entire injected dose. The tissue distribution of technetium -99m - malonate in mice was analyzed with the highest concentration of activity occurring in the kidneys and blood. The liver, spleen, large and small bowels, brain, stomach, lungs, bone, and muscle were also investigated for their content of the labelled complex. Scintiscans were done on rabbits using technetium -99m - malonate to determine the dynamic flow pattern of the complex and to evaluate the scans at various time intervals after injection. A renogram was obtained using the Dyna Camera® to record the pattern of activity through the kidneys. This curve demonstrated that a fast component of excretion with a half-life of 5.5 minutes exists in the rabbit kidney. Absorbed dose calculations were computed for the whole body, kidney, liver, skeleton, and bladder. The bladder component was computed twice, once assuming complete urine retention and again assuming catheterization. The radiation doses were calculated as 26 mrads/ 10 mCi. for the whole body, 159 mrads/10 mCi. for the kidneys, 103 mrads/ 10 mCi. for the liver, 2064 mrads/10 mCi. for the skeleton and 11.9 rads/ 10 mCi. for the bladder assuming complete urinary retention. With the bladder catheterized. the doses fell to: 138 mrads/10 mCi., 43 mrads/ 10 mCi., 103 mrads/10 mCi., and 1.5 mrads/10 mCi. for the kidneys, liver, skeleton, and bladder respectively.

Text

2010-01-28

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http://hdl.handle.net/2429/19294

Pharmaceutical Sciences

University of British Columbia

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