DEVELOPMENT AND UTILIZATION OF A WALKER 256 TUMOR INDUCED OSTEOGENIC SMALL ANIMAL MODEL FOR STUDY OF (TC-99M)DIPHOSPHONATE COMPLEXES (BIODISTRIBUTION, HEDP, HPLC)
Abstract
The objective of this research was to develop and utilize a Walker 256 tumor induced osteogenic small animal model to study ('99m)Tc(NaBH(,4))HEDP complexes. Solid tumor was induced in muscle adjacent to the tibia of Fischer-344 rats by the implantation of Walker 256 carcinoma cells. Histopathological studies confirmed the induction of discrete osteogenesis on the periosteal surface of the tibia. The biodistribution of ('99m)Tc HMDP and ('99m)TC MDP was determined in 18 tumor bearing animals and in the same number of normal animals. The results of the study were found to be comparable with clinical findings in humans. The model was proved to be valid for studying bone imaging agents. Seven ('99m)Tc(NaBH(,4))HEDP complexes were obtained from the separation of a reaction mixture by anion exchange HPLC. Two complexes were treated as a single entity. Six biodistribution studies of ('99m)Tc(NaBH(,4))HEDP complexes were conducted. Each study consisted of two complexes. Each complex was studied twice. Results indicated that each complex had a distinct biodistribution pattern. The complex Z had a little affinity for the bone and was judged to be a complex of different chemical structure and properties. Correlation analyses were conducted with and without the data from the complex Z. Inverse correlations were found between the new bone uptake and the charge and size of the complexes. There were also inverse correlations between these two physical properties and the uptake ratio of new bone to normal bone and new bone to muscle. Direct correlations were found between the new bone uptake and the uptake in the blood, spleen and stomach.
Degree
Ph.D.
Subject Area
Pharmacology
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.