title: Evaluation of dithiol chelating agents as potential adjuvants for anti-IL-2 receptor lead or bismuth alpha radioimmunotherapy.
abstract: The dithiol chelating agents 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for use as potential adjuvants to reduce or prevent radiotoxicity in anti-interleukin-2 receptor (IL-2R) Lead-212 or Bismuth-212 alpha-radioimmunotherapy. 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 DMSA 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 chronic toxicities on blood hematology, blood chemistry or organ weights were observed for treated mice. DMPS and DMSA were effective in accelerating whole body clearance of the gamma-emitting tracer Bismuth-206. Both chelates significantly reduced femur uptake of tracer when compared to nontreated control mice. However, only DMPS prevented early (2 h postinjection) renal accumulation. These studies support the use of DMPS as a potential adjuvant chelation therapy in Lead-212 or Bismuth-212 radioimmunotherapy protocols.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National Naval Medical Center, Bethesda, MD 20889, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Jones
authors.forename: L J
authors.initials: LJ
authors.lastname: Tiffany
authors.forename: K
authors.initials: K
authors.lastname: Garmestani
authors.forename: O A
authors.initials: OA
authors.lastname: Gansow
authors.forename: R W
authors.initials: RW
authors.lastname: Kozak
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001729:Bismuth / Q000493:pharmacokinetics / Q000494:pharmacology*; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002614:Chelating Agents / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D007202:Indicators and Reagents; D007854:Lead / Q000493:pharmacokinetics / Q000494:pharmacology*; D007856:Lead Radioisotopes; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy; D011868:Radioisotopes; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000187:drug effects*; D004113:Succimer / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014494:Unithiol / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D002614:Chelating Agents; D007202:Indicators and Reagents; D007856:Lead Radioisotopes; D011868:Radioisotopes; D015375:Receptors, Interleukin-2; D013438:Sulfhydryl Compounds; D007854:Lead; D014494:Unithiol; D004113:Succimer; D001729:Bismuth