Bone seeker

Abstract: Background: The alpha-emitter 223 Ra, which localizes in osteoblastic active zones, including on skeletal surfaces and in osteoblastic metastases, has recently been introduced as a potential therapeutic agent against skeletal metastases. Here, the adverse effects of high dosages in animals were investigated. Materials and Methods: Balb/c mice received intravenously (i.v.) either 1250, 2500, or 3750 kBq/kg of dissolved 223 RaCl2 and were followed in the initial toxicity phase. At the 4-week end-point, the animals were sacrificed and blood samples were collected to study the effects on clinical chemistry and hematological parameters. Selected organs were weighed and tissue samples examined by microscopy. Results: Treatment with 223 Ra caused a dose-related minimal to moderate depletion of osteocytes and osteoblasts in the bones. Furthermore, a dose-related minimal to marked depletion of the hematopoietic cells in the bone marrow, and a minimal to slight extramedullary hematopoiesis in the spleen and in the mandibular and mesenteric lymph nodes were observed. The LD50 for acute toxicity, defined as death within 4 weeks of receiving the substance, was not reached. Conclusion: This study demonstrated that high doses of the bone-seeker 223 Ra did not completely inactivate the blood-producing cells. The relatively high tolerance to skeletal alpha doses was probably caused by the surviving pockets of red bone marrow cells beyond the range of alpha particles from the bone surfaces, and the recruitment of peripheral stems cells.

Abstract: This paper investigates further the relationship between the initial bone clearance of a bone-seeking radioisotope or labeled substance and the bone blood flow. The bone blood flow of rats was modified over the widest possible range of physiological values by heating and cooling their hindlimbs. Osseous blood flow was measured by the arteriolar trapping of labeled microspheres of 15 micrometer diameter injected into the left ventricle. The plasma clearances of 45Ca and 99 m Tc by bone were measured 10 min after the intravenous injection of radiocalcium and of 99 m technetium pyrophosphate. The extraction ratio for 45Ca over the 10-min interval (45Ca clearance/bone plasma flow) was 0.60 for low blood flows, 0.40 for blood flows at rest, and 0.25 for high values of flow. The data for 99 m Tc were, respectively, 0.68, 0.34, and 0.22. Initial bone clearances of either substance should not be used to measure the increases in bone blood flow over the values at rest.

Abstract: This paper investigates further the relationship between the initial bone clearance of a bone-seeking radioisotope or labeled substance and the bone blood flow. The bone blood flow of rats was modified over the widest possible range of physiological values by heating and cooling their hindlimbs. Osseous blood flow was measured by the arteriolar trapping of labeled microspheres of 15 micrometer diameter injected into the left ventricle. The plasma clearances of 45Ca and 99m Tc by bone were measured 10 min after the intravenous injection of radiocalcium and of 99m technetium pyrophosphate. The extraction ratio for 45Ca over the 10-min interval (45Ca clearance/bone plasma flow) was 0.60 for low blood flows, 0.40 for blood flows at rest, and 0.25 for high values of flow. The data for 99m Tc were, respectively, 0.68, 0.34, and 0.22. Initial bone clearances of either substance should not be used to measure the increases in bone blood flow over the values at rest.