Antunes, Inês F.

Bilewicz, A.

Gano, L.

Majkowska, A.

Neves, M.

Santos, A.

Teixeira, Fatima

Teixeira, Fátima C.

Laboratório Nacional de Energia e Geologia Repository

New indazolebisphosphonates for bone targeted radiotherapy: synthesis, radiolabeling, in vitro and in vivo studies

Repositório do LNEG

Abstracts Search Abstract   Radiopharmacy/Radiochemistry: Therapy - Alpha-Beta Emitters   Monday October 13, 2008  16:00h - 16:30h  Room: Poster Exhibition Area    Bisphosphonates (BPs) are ligands for radioactive metal complexes used for imaging and therapeutic applications. The last BPs generation are heterocyclic nitrogen containing side chain such as risedronate and zoledronate. The aim of this study is to obtain new BPs derived from indazole with high biological and radiopharmaceutical potential activities. We report the synthesis and characterization of new indazolebisphosphonates (IDZBPs) substituted at different C- or N- positions of indazole rings, with the side chain with different lengths (1 to 5 carbon atoms from the bisphosphonate function to the nitrogen atom of the ring). IDZBPs are suitable for complexation with 153Sm and the low energy electron emitters 177Lu and 47Sc. Radiochemicals tagged with low energy electron emitters are preferred because they are more likely to deliver a therapeutic dose to the bone and spare the bone marrow. Hydroxyapatite experiments, have shown that the highest binding values were obtained with [hydroxyl(1H-indazol-3-yl)methanediyl]bis(phosphonic acid) and [hydroxyl(1-methyl-1H-indazol-3-yl)methanediyl]bis(phosphonic acid) complexed by 153Sm, 177Lu and 46Sc. These selected potential radiopharmaceuticals were submitted to biodistribution studies. Inexperiments, we use the scandium radioisotope 46Sc, instead of 47Sc because 47Sc is produced usingfast neutrons via the reaction 47Ti (n,p)47Sc, which is not easily accessible to us, while 46Sc is producing by direct neutron irradiation of scandium. 153Sm and 177Lu were respectively produced by direct neutron irradiation of enriched samarium (98%) and natural lutetium oxides. A slight change between the two ligands - the free N-H position substituted by a methyl group - results in a distinct radiopharmacokinetic. These experiments confirm that a single change in the chemical structure plays a decisive role in binding to hydroxyapatite, as well in bone uptake. Acknowledgements: This work was carried out in the frame of Marie Curie Action for the Transfer of Knowledge, contract No. MTKD-CT-2004-509224, European Commission, FCT- Portuguese Foundation for Science and Technology (FEDER and POCI/QUI/55508/2004)and Ministry of Science and Higher Education of Poland 7T09A07320.  « back « backP438 New indazolebisphosphonates for bone targeted radiotherapy: synthesis, radiolabeling, in vitro and in vivo studies  M. Neves1, L. Gano1, F. C. Teixeira2, I. Antunes2, A. Santos3, A. Majkowska4, A. Bilewicz4; 1Instituto Tecnologico Nuclear, Sacavém, PORTUGAL, 2Instituto Nacional de Engenharia, Tecnologia e Inovação, Lisboa, PORTUGAL, 3Instituto Biomédico de Investigação da Luz e Imagem, Coimbra, PORTUGAL, 4Institute of Nuclear Chemistry, Warsaw, POLAND.  EANM Executive Secretariat info@eanm.org Phone: +43-1-212 80 30 Fax: +43-1-212 80 309

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New indazolebisphosphonates for bone targeted radiotherapy: synthesis, radiolabeling, in vitro and in vivo studies

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