Ovarian cancer often leads to metastases which are initially confined to the intraperitoneal (i.p.) space. Alpha-particle (α)-emitting radionuclides are a promising therapy against such metastases; their short path length will spare adjacent normal tissue while the high local energy deposition is effective at sterilizing targeted cells. Because ovarian cancer metastases are initially confined to the intraperitoneal (i.p.) space, they can be targeted using liposomes immunolabeled with the humanized monoclonal antibody, trastuzumab (Herceptin) that are injected directly into the i.p. cavity.

Previous work has shown maximal encapsulation of 10% of the Ac-225 using passive encapsulation (Sofou et al. J Nuclear Medicine 45:253-260, 2004). In this work, Ac-225 was actively loaded (Chang et al. Cancer Biotherapy & Radiopharmaceuticals 21:394, 2006) into dinonodecanoyl-glycero-phosphatidylcholine:cholesterol (DNPC:Chol, 2:1 molar ratio) liposomes containing polyethyleneglycol (PEG, 5 mol %) using the ionophore calcimycin. This method resulted in up to 65% encapsulation efficiency. These liposomes were then incubated at 37ºC and 5% CO₂ in cell culture media (RPMI) with and without serum. Liposome samples were removed at 24 hours, then weekly for 4 weeks, at which time liposomes retained between 60-80% of their initial activity. During this time, dynamic light scattering measurements were performed on the same samples, showing that liposome size remained stable as well. In vivo, nude mice were injected i.p. with 5x10⁶ SKOV3 ovarian carcinoma cells, which developed into tumor nodules on organs in the i.p. space. Two weeks post-injection, immunoliposomes were injected for imaging studies. Immunoliposomes were loaded with In-111 for μSPECT/CT imaging studies and fluorescence imaging was done utilizing a rhodamine-labeled lipid in the liposome structure. Imaging analysis demonstrated that liposomes were selectively targeted to the sites of tumor nodules. These findings indicate the potential of these systems for targeted delivery of radionuclides with little expected binding to normal cells. Immunoliposomes may be a promising tool for targeted delivery of radionuclides to these metastatic nodules before neovascularization occurs.