Bioavailability of 99mTc-Ha-paclitaxel complex [99mTc-ONCOFID-P] in mice using four different administration routes
✍ Scribed by Laura Meléndez-Alafort; Mattia Riondato; Anna Nadali; Alessandra Banzato; Davide Camporese; Pasquale Boccaccio; Nikolay Uzunov; Antonio Rosato; Ulderico Mazzi
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- French
- Weight
- 335 KB
- Volume
- 49
- Category
- Article
- ISSN
- 0022-2135
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✦ Synopsis
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 ^99m^Tc by the addition of ^99m^Tc‐pertechnetate, SnCl~2~ and sodium gluconate. The reaction mixture was incubated for 90 min at 65°C and purified by size exclusion chromatography. The obtained ^99m^Tc‐ONCOFID‐P had 100% radiochemical purity and was stable in a phosphate buffer dilution 1:100 for 6 h at 37°C. ^99m^Tc‐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 ^99m^Tc‐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. Copyright © 2006 John Wiley & Sons, Ltd.