Therapy of Ovarian Carcinoma by Targeted Delivery of Alpha-Particles Using Immunoliposomes Capable of Retaining Alpha-Emitting Daughters
Abstract
The objective of this work is to develop a liposomal system for encapsulating alphaparticle emitting radionuclides for use in IP-administered targeted therapy of ovarian cancer metastases. The scope of the overall project includes development, stability, and radionuclide retention testing of the liposomes as well as the evaluation of their targeting properties, in vitro, and in vivo (aims 1 and 2). This is to be followed by evaluation of tumor cell kill using monolayer cell culture, spheroid culture and in tumorbearing animals (aims 3 and 4). Substantial progress has been made towards achieving aims 1 and 2. Stable liposomes of different sizes and charge were prepared. Actinium-225 retention was more than 88% over 30 days. Liposomes were successfully conjugated to trastuzumab, an anti-HER2/neu antibody. A 53-fold increase in HER2/neu+ cell binding was observed for the radioimmunoliposomes compared to non-targeted liposomes. 56% of the cell-associated radioimmunoliposomes were internalized. Studies, in vivo, yielded 21.3+/-19.5%ID/g tumor uptake at 4 hrs ppst-injection (PI); liver (3.9-24.9%ID/g) and spleen (130.6-296.3%ID/g) accumulation of liposomes was observed at 8 hrs PI. Fluorescent liposomes were detected in intact form in the peritoneal cavity 6 hrs after administration. Efficacy evaluations will be performed in the next 2 years.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA431313
Entities
People
- George Sgouros
Organizations
- Johns Hopkins University