title: Nanozeolite bioconjugates labeled with223Ra for targeted alpha therapy.
abstract: BACKGROUND
  Alpha particle emitting isotopes are of considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Among the many α emitters,223Ra exhibits very attractive nuclear properties for application in radionuclide therapy. The decay of this radioisotope and its daughters is accompanied by the emission of four α-particles, releasing 27.9MeV of cumulative energy. Unfortunately the lack of an appropriate bifunctional ligand for radium has so far been a main obstacle for the application of223Ra in receptor targeted therapy. In our studies we investigated the use of nanozeolite-Substance P bioconjugates as vehicles for223Ra radionuclides for targeted α therapy.
  
  
  METHODS
  The sodium form of an A-type of nanozeolite (NaA) was synthesized using the template method. Next, the nanozeolite particles were conjugated to the Substance P (5-11) peptide fragment, which targets NK-1 receptors on glioma cells. The obtained bioconjugate was characterized by transmission emission spectroscopy, thermogravimetric analysis and dynamic light scattering analysis. The NaA-silane-PEG-SP(5-11) bioconjugates were labeled with223Ra by exchange of the Na+cation and the stability, receptor affinity and cytotoxicity of the obtained radiobioconjugates were tested.
  
  
  RESULTS
  The223Ra-labeled nanozeolite bioconjugate almost quantitatively retains223Ra in vitro after 6days, while the retention of decay products varies from 90 to 95%. The synthesized223RaA-silane-PEG-SP(5-11) showed high receptor affinity toward NK-1 receptor expressing glioma cells and exhibited a high cytotoxic effect in vitro.
  
  
  CONCLUSIONS
  Substance P functionalized nanozeolite-A represents a viable solution for the use of the223Ra in vivo generator as a therapeutic construct for targeting glioma cells.
authors.affiliation: Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Piotrowska
authors.affiliation: Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Męczyńska-Wielgosz
authors.affiliation: Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Majkowska-Pilip
authors.affiliation: Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Koźmiński
authors.affiliation: Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wójciuk
authors.affiliation: Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Cędrowska
authors.affiliation: Institute for Transuranium Elements, Joint Research Centre - European Commission, 76125 Karlsruhe, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bruchertseifer
authors.affiliation: Institute for Transuranium Elements, Joint Research Centre - European Commission, 76125 Karlsruhe, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Morgenstern
authors.affiliation: Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland; Faculty of Medicine, University of Information Technology and Management in Rzeszów, ul. Sucharskiego 2, 35-225 Rzeszów, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kruszewski
authors.affiliation: Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland. Electronic address: a.bilewicz@ichtj.waw.pl.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Bilewicz
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007553:Isotope Labeling; D049329:Nanostructures; D011883:Radium / Q000627:therapeutic use*; D017641:Zeolites / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D017641:Zeolites; D011883:Radium
keywords: Alpha emitters; Glioma; Radionuclide therapy; Zeolite nanoparticles