Mobilization of radioactive strontium from mouse and rat using dicarboxylic acid derivatives of cryptand (2.2)

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 N,N'-disubstituted derivatives of 1,4,10,13-tetraoxa-7,16-diaza-cyclooctadecane(crypt and 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.