To date, there has been no effective therapy to counter incorporated radionuclides of strontium. In an endeavour to solve this problem, we have synthesized and evaluated various NN'-disubstituted derivatives of 1,4,10,13-tetraoxa-7,16-diaza-cyclooctadecane (cryptand 2.2) for their ability to mobilize 85Sr2+. These ligands are water soluble and have a relatively low acute i.v. toxicity, as demonstrated by their evaluation in rat and mouse. The di-sodium-calcium complex and tetra-sodium salt of the cryptand (2.2) dimalonate have exerted a remarkable decorporation effectiveness for 85Sr2+ in extracellular space. The tetra-potassium salt of the cryptand (2.2) dimalonate has a moderate effect, while no mobilization activity can be detected with the cryptand (2.2) that does not have a side chain substituent. Animals were initially given 85SrCl2 either i.p. or into the lung, then the compounds were administered 30-60 min later using an alternative route. The degree of decorporation achieved a 80-95% of the initial body burden (ibb) compared with the control values of 20-30%. The agents are resorbed easily from the lung, and the radiostrontium deposition in bone was inhibited strongly by a decorporation agent. The success of the treatment, however, is dependent upon the speed with which decorporation therapy commences.
ASJC Scopus subject areas
- Radiological and Ultrasound Technology
- Radiology Nuclear Medicine and imaging