Investigation of technetium methylene diphosphonate bone imaging agents
Abstract
A high-performance liquid chromatographic method has been developed to quantify total pertechnetate concentration, i.e., $\sp{\rm 99m}$Tc + $\sp{99}$Tc, in the eluent of a $\sp{99}$Mo/$\sp{\rm 99m}$Tc generator. Detection of pertechnetate is based on its UV-absorbance, and not on its radioactivity. The ion-pairing reversed-phase chromatographic method also allows for the profiling of generator eluent to determine chemical and radiochemical purity. The ion-pairing reversed-phase chromatographic procedure which was developed has been applied to the separation of components formed in the preparation of commercial bone imaging radiopharmaceutical kits. Separation of these Tc(Sn)-diphosphonate complexes on silica bound C-18 packing material was demonstrated to be an excellent method of investigating the distribution of products in the reaction mixture as a function of time. The commercial products of three different manufacturers were studied. All showed multiple chromatographically separable components. A feasibility study was carried out to develop a procedure for the labeling and quantification of trace levels of diphosphonate with $\sp{\rm 99m}$Tc. This study successfully labeled a proprietary diphosphonate at the 10-ppt level. The actual labeling of the diphosphonate proceeded through a ligand-exchange reaction with a proposed Tc-acetate intermediate. Labeling at lower levels was not possible due to the slow kinetics involved in the exchange reaction. Ligand-to-metal ratios of several Tc-formate complexes were determined by an indirect dual-isotope labeling method. Results of this study indicated ligand-to-metal ratios ranging from 0.7 to 4.0. Tc-formate species were proposed as suitable ligand exchange precursors in the preparation of Tc-diphosphonate complexes. A study of the kinetics of this exchange with methylene diphosphonic acid indicates a pseudo-first-order rate constant of 1 $\times$ 10$\sp{-4}$ sec$\sp{-1}$. The product of the ligand exchange production of Tc-MDP, was compared to products formed in the Tc(Sn)-MDP commercial kits. Both production methods yielded a component with absorption maximum of 404 nm, and showed similar retention behavior upon chromatographic evaluation.
Degree
Ph.D.
Advisors
Pinkerton, Purdue University.
Subject Area
Analytical chemistry
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