Tissue and Subcellular Distribution of Bismuth Radiotracer in the Rat: Considerations of Cytotoxicity and Microdosimetry for Bismuth Radiopharmaceuticals

Abstract

The whole-body clearance, organ distribution, and subcellular distribution of no-carrier-added and carried-added intraperitoneally administered bismuth radiotracers (205Bi-206Bi) has been determined in Sprague-Dawley rats. Differences in clearance rate kinetics were observed for this study with the administration of neutral solutions of tracers in a carbonate buffer compared to other studies with other chemical forms. The final organ distribution was not strongly dependent on administered chemical form. We provide definitive evidence that bismuth does indeed enter subcellular organelles such as the nucleus and the mitochondria, which had 30-50% and 10-25%, respectively, of activity in kidney tissue. The kidneys were the main sink for radiotracer with uptake ranging from 20 to 50% of total body activity. The calculated energy deposition by recoil nuclei after alpha emission of potentially therapeutically useful 212Bi was found to equal or exceed the alpha energy deposition per organelle if the source is inside the cell nucleus or mitochondria.

Transformation of Human Osteoblast Cells to the Tumorigenic Phenotype by Depleted Uranium-Uranyl Chloride

“…Despite the wellknown low solubility of uranyl compounds, we found cellular uptake of uranium consistent with other transuranic compounds (39 DU-U02+ appears to have transforming ability slightly greater than that of many other trace heavy metals, which also induce neoplastic cell transformation in vitro, as well as cause tumor formation in animals (40). While additional animal studies are needed to address the effect of protracted exposure and tumor induction in vivo, the implication from our model system study is that the risk of neoplastic induction from internalized DU exposure may be similar to other biologically reactive and carcinogenic heavy metal compounds such as lead and nickel.…”

Pharmacokinetics and Toxicity of Bismuth Compounds

“…The highest concentration/g wet weight was always found in the kidne y, largely independent of the compound adm inistered or the route ofadministration (Badinand & Quincy 1959;Hall & Farber 1972;Hursch & Brown 1969;Lechat et al 1976;Pieri & Wegmann 1981;Russ et al 1975;Sollmann et al 1938;Sollmann & Seifter 1942;van der Werff 1965;Vienet et al 1983;Zidenberg-Cherr et al 1987). The highest concentration/g wet weight was always found in the kidne y, largely independent of the compound adm inistered or the route ofadministration (Badinand & Quincy 1959;Hall & Farber 1972;Hursch & Brown 1969;Lechat et al 1976;Pieri & Wegmann 1981;Russ et al 1975;Sollmann et al 1938;Sollmann & Seifter 1942;van der Werff 1965;Vienet et al 1983;Zidenberg-Cherr et al 1987).…”

Pharmacokinetics and toxicity of 213Bi-labeled PAI2 in preclinical targeted alpha therapy for cancer

“…In addition to that, free bismuth-213 leached from unstable ACs is also incorporated to some extent into kidney cells. 12 Radiation nephropathy in mice was observed for 9.25 MBq of 213 Bi-DOTA-biotin 13 and for 10 MBq of 213 Bi-Fab' 14 at six months. Some mild chronic nephropathy was observed for 11.4 MBq of 213 Bi-DOTATOC.…”