Therapy of Ovarian Carcinoma by Targeted Delivery of Alpha-Particles Using Immunoliposomes Capable of Retaining Alpha-Emitting Daughters.

摘要

The objective of this work is to develop a liposomal system for encapsulating alpha-particle 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 tumor-bearing animals (aims 3 and 4). In the first progress report, completion of Task 1 and the majority of Task 2 was reported. Although retention of the parent, 225Ac was 88%, retention of 213Bi, the last daughter in the decay chain was only 4 to 5% after 30 days (JNM '04). The previous report ended with a brief description of a novel liposomal construct (multi-vesicular liposome - MUVEL) that had been engineered to address the known reasons for low 213Bi retention. Over the past year, this new construct has been characterized, both, in vitro and in vivo. Although not as large as expected theoretically, the MUVEL structures increased 213Bi retention from 5% to 18%. Animal studies demonstrated tumor to kidney ratios that were comparable to Ac-225-labeled antibody, however. Preloading of liposomes to reduce RES uptake will be investigated improve this ratio as the work moves to efficacy and toxicity studies in year 3.