THE ACCUMULATION OF SYNTHETIC CHELATING AGENTS IN OSSEOUS TISSUES

¹ Pharmaceutical Chemistry and Isotope Departments, The Weizmann Institute of Science, Rehovoth, Israel

The biologic behavior of synthetic chelating agents (derivatives of iminodiacetic acid) and their affinity for bone were studied in vitro and in vivo in short-term experiments. In vitro experiments indicate that the affinity of different synthetic amino acids for bone is a function of their ability to form chelates with calcium. In vivo experiments show that, following intraperitoneal injection into young rats, only those amino acids which are able to complex calcium (log stability constants for their calcium complexes in the range of 3 to 5 at 30°C, µ = 0.1) will selectively Concentrate in mineralized areas of bone tissue. The affinity towards chelating agents of the various bone tissues studied varies with their metabolic activity, the accumulation of chelates being greatest at the sites of very active bone formation (the region of the epiphysial plates and the callus). The synthetic amino acids are cleared rapidly from the body, mainly through the kidney, and are excreted unchanged in the urine. By means of vital staining and autoradiography of bones it was found that the pattern of uptake of the labeled synthetic chelating agents and of alizarin and Ca⁴⁵ ion in bones was similar. The experimental results suggest that the mechanism of deposition of the synthetic organic bone-seekers in bone is that of a chelation process which probably takes place at the surface of bone mineral between the amino acids and the calcium ions. It was suggested that chelating agents of the iminodiacetic acid type may serve as vital indicators of the metabolic activity of bone as manifested in surface exchange and chelation processes.