CHARACTERIZATION OF TECHNETIUM HYDROXYETHYLIDENE DIPHOSPHONATE COMPLEXES PREPARED BY SODIUM BOROHYDRIDE REDUCTION (ION-EXCHANGE, CHARGE, POLYNUCLEAR)
Abstract
The fundamental solution chemistry and biodistribution of technetium hydroxyethylidene diphosphonate complexes (Tc-HEDP), prepared by the sodium borohydride reduction of pertechnetate in the presence of the ligand, has been investigated. An anion-exchange high-performance liquid chromatography separation was developed that allowed the individual Tc-HEDP complexes to be isolated and studied. Complimentary HPLC detection schemes were employed, including fixed wavelength UV-visible spectrophotometric detection and/or radiometric detection of ('99m)Tc. Characteristic UV-visible spectra were obtained for many of the Tc-HEDP complexes by utilizing UV-visible photodiode array HPLC detection. The charge on twelve of the Tc-HEDP complexes was determined by anion-exchange HPLC. The separated Tc-HEDP complexes, each assumed to be polyprotic, yielded average charges ranging from -1.5 to -8.0. Approximate hydrated partial molar volumes were determined to range between 560 and 1800 mL/mol. In several cases, as predicted by the ion-exchange theory, a reversal of HPLC elution order was observed as a result of size discrimination. From these results and size-exclusion chromatography data, a polynuclear hypothesis regarding the structure of the complexes has been developed. The biodistribution of six of the ('99m)Tc-HEDP complexes separated by anion-exchange HPLC was studied. An inverse structure-activity correlation was determined to exist between ('99m)Tc uptake in new (lesion) bone and the physical properties, anionic charge and partial molar volume, of the complexes. The uptake in the lesion bone was found to be inversely related to the charge and/or size of the complexes. The results were consistent with the polynuclear hypothesis previously suggested for the Tc-HEDP complexes. A new Tc-formate system was studied with the prospect that it might serve as a ligand-exchange precursor to the synthetic preparation and characterization of the Tc-HEDP complexes. As a direct result of the investigation of the Tc-formate system, it was possible to obtain preliminary fast atom bombardment mass spectrometry results on two of the Tc-HEDP complexes and to establish the experimental parameters required to determine the ligand-to-metal ratio of the Tc-HEDP complexes with ('14)C-labeled HEDP.
Degree
Ph.D.
Subject Area
Analytical chemistry
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