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 r adionuclides of strontium. In an endeavour to solve this problem, we h ave synthesized and evaluated various N,N'-disubstituted derivatives o f 1,4,10,13-tetraoxa-7,1 6-diaza-cyclooctadecane (cryptand 2.2) for th eir ability to mobilize Sr-85(2+). These ligands are water soluble and have a relatively low acute i.v. toxicity, as demonstrated by their e valuation in rat and mouse. The di-sodium-calcium complex and tetra-so dium salt of the cryptand (2.2) dimalonate have exerted a remarkable d ecorporation effectiveness for Sr-85(2+) in extracellular space. The t etra-potassium salt of the cryptand (2.2) dimalonate has a moderate ef fect, while no mobilization activity can be detected with the cryptand (2.2) that does not have a side chain substituent. Animals were initi ally given (SrCl2)-Sr-85 either i.p. or into the lung, then the compou nds 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 resorb ed easily from the lung, and the radiostrontium deposition in bone was inhibited strongly by a decorporation agent. The success of the treat ment, however, is dependent upon the speed with which decorporation th erapy commences.