PREPARATION AND BIOLOGICAL DISTRIBUTION OF TECHNETIUM DIPHOSPHONATE RADIOTRACERS SYNTHESIZED WITHOUT STANNOUS ION

Abstract

Two HEDP [(1-hydroxyethylidene)diphosphonate] complexes of Tc (99Tc or a mixture of 99Tc and 99mTc) were prepared without the use of stannous ion. Tc(NaBH4)-HEDP is synthesized by reduction of TcO4- with NaBH4 in the presence of excess HEDP: this is analogous to the preparation of Tc(Sn)-HEDP in commercial kits wherein Sn(II) functions as the reductant. Tc-HEDP is prepared by substitution of HEDP onto the pre-formed, pre-reduced, Tc center TcBr62-. The HEDP-to-Tc ratio in Tc-HEDP was found to be 1.0 by double-labeling procedures (99Tc and [3H]HEDP), implying that in solution this material is polymeric or at least dimeric. Preparations of Tc(NaBH4)-HEDP and Tc-HEDP with 99mTc are excellent bone-imaging agents in rats and dogs. Tissue distribution studies in rats show that uptake of Tc(NaBH4)-HEDP and Tc-HEDP by the bone is at least equivalent to that achieved by Tc(Sn)-HEDP prepared in commercial kits with Sn(II) as the reductant. Sn is not necessary for the bone-seeking properties of Tc(Sn)-HEDP and the in vivo distribution of a given HEDP radiotracer depends primarily on the presence of the HEDP ligand and not on the nature of the Tc complex itself. Synthesis of Tc radiotracers by a substitution route, rather than by redox, is practicable; this route has the potential of introducing hitherto unattainable flexibility and subtlety into the preparation of Tc radiotracers.