title: N-4-iodophenyl-N'-2-chloroethylurea, a novel potential anticancer agent with colon-specific accumulation: radioiodination and comparative in vivo biodistribution profiles.
abstract: In a search for more selective anticancer drugs, we have designed nitrogen mustard and nitrosourea conjugates leading to a series of N-4-aryl-N'-2-chloroethylureas (CEUs). The iodinated derivative N-4-iodophenyl-N'-2-chloroethylurea (4-ICEU) has demonstrated significant antineoplastic and antiangiogenic potency in preclinical evaluations. In this study, 4-ICEU was radiolabelled with [(125)I]iodide in order to carry out a comparative study of its in vivo behavior profile. 4-[(125)I]-ICEU was synthesized by direct electrophilic radioiodination with 80% radiochemical yield and 97% radiopurity. Three different routes of administration (intraperitoneal (ip), intravenous (iv) and intratumoral (it)) were tested in mice bearing subcutaneously implanted CT-26 murine colon carcinoma. The results clearly established that 4-ICEU was more stable to biotransformation than previously studied CEUs congeners. It was readily bioavailable and reached the CT-26 colorectal tumor regardless of the route of administration. Additionally, the colon mucosa was an important target tissue where 4-ICEU accumulated and remained largely untransformed. In conclusion, these results justify further investigations for developing 4-ICEU as a new chemotherapeutic agent for colorectal cancer.
authors.affiliation: INSERM UMR 484, EA 4231, BP 184, 63005, Clermont-Ferrand, France. emmanuelle.mounetou@inserm.fr
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mounetou
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Miot-Noirault
authors.forename: René C
authors.initials: RC
authors.lastname: Gaudreault
authors.forename: J Claude
authors.initials: JC
authors.lastname: Madelmont
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001345:Autoradiography; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000097:blood / Q000473:pathology; D004355:Drug Stability; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009928:Organ Specificity / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; C527419:iodophenyl-chloroethyl urea; C007685:ethylurea; D014508:Urea