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- Title
Evaluation of Liposomal Radiochemotherapy for Treatment of Cancer.
- Authors
Jonasdottir, T. J.; Borrebæk, J.; Bruland, ØS; Salberg, G.; Moe, L.; Larsen, R. H.
- Abstract
Pegylated liposomes target solid tumors by exploiting the capillary leakage properties of tumor neovasculature. The goal of the study was to investigate distribution and tumor targeting properties of the alpha-particle emitter223Ra, encapsulated in doxorubicin-containing-liposomes(Caelyx®/Doxil®).Caelyx® was given before the injection of liposomal223Ra to reduce the reticulo-endothelial-system uptake. A pilot study was conducted to determine the optimal time interval between the pre-treatment/treatment. Subsequently a more extensive distribution study was performed in normal BalbC mice. In addition, distribution and tumor uptake was evaluated in a human osteosarcoma xenograft mice model and in a dog with spontaneous osteosarcoma.Optimal blood-to-liver and blood-to-spleen ratios of liposomal radium was achieved in animals that received pre-treatment with Caelyx® 4 days in advance. Blood clearance was relatively slow, in mice t1/2 was∼28 h(BalbC mice) and in the dog t1/2 was∼ 39 h. In mice the liver uptake appeared to be relatively low in contrast to the spleen, where there was a significant uptake. In the dog the uptake in both liver and spleen was moderate. In the xenograft model there was generally a higher retention of activity in the tumor vs. soft tissue. In the dog the 24 h uptake was considerably higher in both calcified and non-calcified tumor metastases of different organs, than in normal tissue.Liposomal223Ra has a relevant biodistribution and blood clearance for tumor targeting. More extensive future studies are supported by the favourable tumor/normal-tissue ratio in a dog with spontaneous osteosarcoma.
- Subjects
CANCER treatment; DRUG therapy; LIPOSOMES; TUMORS; OSTEOSARCOMA; LABORATORY rats
- Publication
Veterinary & Comparative Oncology, 2005, Vol 3, Issue 1, p58
- ISSN
1476-5810
- Publication type
Article
- DOI
10.1111/j.1476-5810.2005.064an.x