EVALUATION OF DITHIOL CHELATING-AGENTS AS POTENTIAL ADJUVANTS FOR ANTI-IL-2 RECEPTOR LEAD OR BISMUTH ALPHA-RADIOIMMUNOTHERAPY

The dithiol chelating agents 2,3-dimercapto-1-propanesulfonic acid (DM PS) and meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for use as potential adjuvants to reduce or prevent radiotoxicity in anti int erleukin 2 receptor (IL-2R) Lead-212 or Bismuth-212 alpha-radioimmunot herapy. DMPS was less toxic than DMSA to tumor cell lines in culture. No adverse effects on the ability of an anti-IL-2R monoclonal antibody (MAb) to bind to its specific antigen were detected using DMPS or DMS A at concentrations up to 600 ug/mL in 10% or 100% mouse serum. After a 5-day oral administration of chelating agent, neither acute nor chro nic toxicities on blood hematology, blood chemistry or organ weights w ere observed for treated mice. DMPS and DMSA were effective in acceler ating whole body clearance of the gamma-emitting tracer Bismuth-206. B oth chelates significantly reduced femur uptake of tracer when compare d to nontreated control mice. However, only DMPS prevented early (2 h postinjection) renal accumulation. These studies support the use of DM PS as a potential adjuvant chelation therapy in Lead-212 or Bismuth-21 2 radioimmunotherapy protocols.