title: Mobilization of radioactive strontium from mouse and rat using dicarboxylic acid derivatives of cryptand (2.2).
abstract: 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.
authors.affiliation: Frédéric Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary.
authors.forename: L P
authors.initials: LP
authors.lastname: Varga
authors.forename: L B
authors.initials: LB
authors.lastname: Sztanyik
authors.forename: E
authors.initials: E
authors.lastname: Rónai
authors.forename: K
authors.initials: K
authors.lastname: Bodó
authors.forename: E
authors.initials: E
authors.lastname: Brücher
authors.forename: B
authors.initials: B
authors.lastname: Györi
authors.forename: J
authors.initials: J
authors.lastname: Emri
authors.forename: Z
authors.initials: Z
authors.lastname: Kovács
mesh_terms: D000818:Animals; D002614:Chelating Agents; D043844:Crown Ethers; D004988:Ethers, Cyclic / Q000737:chemistry*; D005260:Female; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013326:Strontium Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D002614:Chelating Agents; D043844:Crown Ethers; D004988:Ethers, Cyclic; D013326:Strontium Radioisotopes; C089738:cryptand 2.2