title: Cancer radioimmunotherapy with alpha-emitting nuclides.
abstract: In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with beta-emitters for the treatment of refractory cases. The development of novel RIT with alpha-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with alpha-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of alpha-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an alpha-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with alpha-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of alpha-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies.
authors.affiliation: INSERM U 601, quai Moncousu, Nantes, 44035, France. coutur@nantes.inserm.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Couturier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Supiot
authors.forename: Marie
authors.initials: M
authors.lastname: Degraef-Mougin
authors.forename: Alain
authors.initials: A
authors.lastname: Faivre-Chauvet
authors.forename: Thomas
authors.initials: T
authors.lastname: Carlier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Chatal
authors.forename: François
authors.initials: F
authors.lastname: Davodeau
authors.forename: Michel
authors.initials: M
authors.lastname: Cherel
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use*; D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods* / Q000639:trends*; D011868:Radioisotopes / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000627:therapeutic use
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals