Bioavailability of 99mTc-Ha-paclitaxel complex [ 99mTc-ONCOFID-P] in mice using four different administration routes

Laura Meléndez-Alafort, Mattia Riondato, Anna Nadali, Alessandra Banzato, Davide Camporese, Pasquale Boccaccio, Nikolay Uzunov, Antonio Rosato, Ulderico Mazzi

Research output: Contribution to journalArticle

Abstract

Paclitaxel, an anti-tumour drug, shows good results against breast and ovarian cancer. However, its therapeutic response is associated with toxic side-effects caused by the agent used to dissolve it. Recently paclitaxel was linked to the linear polysaccharide hyaluronic acid (HA), showing good solubility, stabilization, localization and a reduction of cytotoxic side-effects. To study potential therapeutic applications, HA-paclitaxel bioconjugate (ONCOFID-P) was labelled with 99mTc by the addition of 99mTc-pertechnetate, SnCl2 and sodium gluconate. The reaction mixture was incubated for 90 min at 65°C and purified by size exclusion chromatography. The obtained 99mTc-ONCOFID-P had 100% radiochemical purity and was stable in a phosphate buffer dilution 1:100 for 6 h at 37°C. 99mTc-ONCOFID-P bioavailability studies were carried out in healthy mice using four different administration pathways. The analysis showed that after intravenous administration more than 80% of the injected radiopharmaceutical was found in liver and spleen. Intraperitoneal, intravesical and oral administrations showed that all the 99mTc-ONCOFID-P remained at the administration site. These results demonstrate that ONCOFID-P administered intravenously could be used for liver metastasis therapy due to its high physiological and receptor-specific liver uptake, while intravesical, intraperitoneal and oral administration of ONCOFID-P could be used for local treatment of superficial cancers.

Original languageEnglish
Pages (from-to)939-950
Number of pages12
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume49
Issue number11
DOIs
Publication statusPublished - Oct 15 2006

Keywords

  • Tc-ONCOFID-P
  • Anti-neoplastic drug
  • Hyaluronic acid
  • ONCOFID-P
  • Paclitaxel

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Organic Chemistry
  • Clinical Biochemistry
  • Molecular Medicine
  • Pharmacology

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    Meléndez-Alafort, L., Riondato, M., Nadali, A., Banzato, A., Camporese, D., Boccaccio, P., Uzunov, N., Rosato, A., & Mazzi, U. (2006). Bioavailability of 99mTc-Ha-paclitaxel complex [ 99mTc-ONCOFID-P] in mice using four different administration routes. Journal of Labelled Compounds and Radiopharmaceuticals, 49(11), 939-950. https://doi.org/10.1002/jlcr.1107