title: [177Lu]pertuzumab: experimental therapy of HER-2-expressing xenografts.
abstract: Pertuzumab (Omnitarg) is a novel antibody against HER-2, domain II. HER-2 is a tyrosine kinase receptor that is overexpressed in several carcinomas, especially breast cancer. Pertuzumab, labeled with the low-energy beta emitter (177)Lu, might be a candidate for targeted radiotherapy of disseminated HER-2-positive micrometastases. The radiolabeled antibody [(177)Lu]pertuzumab showed favorable targeting properties in BALB/c (nu/nu) mice with HER-2-overexpressing xenografts. The absorbed dose in tumors was more than five times higher than the absorbed dose in blood and more than seven times the absorbed dose in any other normal organ. Experimental therapy showed that [(177)Lu]pertuzumab delayed tumor progression compared with controls (no treatment, P < 0.0001; nonlabeled pertuzumab antibody, P < 0.0001; and (177)Lu-labeled irrelevant antibody, P < 0.01). No adverse side effects of the treatment could be detected. Thus, the experimental results support the planning of clinical studies applying [(177)Lu]pertuzumab for therapy.
authors.affiliation: Department of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden. mikael.persson@bms.uu.se
authors.forename: Mikael
authors.initials: M
authors.lastname: Persson
authors.forename: Lars
authors.initials: L
authors.lastname: Gedda
authors.forename: Hans
authors.initials: H
authors.lastname: Lundqvist
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Hans
authors.initials: H
authors.lastname: Nordgren
authors.forename: Per-Uno
authors.initials: PU
authors.lastname: Malmström
authors.forename: Jörgen
authors.initials: J
authors.lastname: Carlsson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D001610:Beta Particles; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008187:Lutetium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D011868:Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000922:Immunotoxins; D011868:Radioisotopes; D008187:Lutetium; C485206:pertuzumab