Delivery of liposome-membrane associated anticancer agents to solid tumors exemplified by Camptothecin liposomes

This project aims at investigating the incorporation of poorly water-soluble cytostatics like Camptothecin (CPT) and its lipophilic derivatives within liposomes, focusing on the in-vivo behaviour of these formulations in animals and the ability of the lip osomes to specifically deliver CPTs to solid tumors and thus reduce the side effects seen from these anticancer drugs. In earlier studies of the applicant, solid experience has been acquired in preparation and in-vitro characterisation of CPT-liposomes. E xpertise in antitumor efficacy studies in nude mice bearing human xenografts shall now be acquired during a one-year research visit at the Tumor Biology Center, Freiburg, Germany. The expertise offered there is regarded essential for further developing th e personal skills of the candidate as well as extending the methodological reservoir of the "drug transport and drug delivery"- research team at the University of Tromsø. The analytical methods and xenograft models in nude mice acquired in Freiburg shall be established and used for comparable studies at our facilities at the University of Tromsø. The targeting mechanism of the CPT-liposomes in vivo, will be studied further in rats by Quantitative Whole Body Autoradiography (QWBA) and by live in vivo distr ibution studies using Positron Emission Tomography (PET). The work involves development of radiolabelling mechanisms for camptothecin as well as for the liposome. A dual radiolabelling technique using 14C and 125I for the QWBA studies are planed and 18F o r 11C will be used for PET imaging.