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|Title:||Nanozeolite bioconjugates labeled with 223Ra for targeted alpha therapy|
|Authors:||PIOTROWSKA A; MECYNSKA-WIELGOSZ Sylwia; MAJKOWSKA PILIP Agnieszka; KOZMINSKI P; WOJCIUK Grzegorz; CEDROWSKA Edyta; BRUCHERTSEIFER Frank; MORGENSTERN Alfred; KRUSZEWSKI M.; BILEWICZ Aleksander|
|Citation:||NUCLEAR MEDICINE AND BIOLOGY vol. 47 p. 10-18|
|Publisher:||ELSEVIER SCIENCE INC|
|Type:||Articles in periodicals and books|
|Abstract:||Introduction: 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 27.9 MeV of cumulative energy. Unfortunately the lack of an appropriate bifunctional ligand for radium has so far been a main obstacle for the application of 223Ra in receptor targeted therapy. In our studies we investigated the use of nanozeolite–Substance P bioconjugates as vehicles for 223Ra 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 with 223Ra by exchange of the Na+ cation and the stability, receptor affinity and cytotoxicity of the obtained radiobioconjugates were tested. Results: The 223Ra-labeled nanozeolite bioconjugate almost quantitatively retains 223Ra in vitro after 6 days, while the retention of decay products varies from 90 to 95%. The synthesized 223RaA–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 the 223Ra in vivo generator as a therapeutic construct for targeting glioma cells.|
|JRC Directorate:||Nuclear Safety and Security|
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