Premium
Evaluation of Liposomal Radiochemotherapy for Treatment of Cancer
Author(s) -
Jonasdottir T. J.,
Borrebæk J.,
Bruland ØS,
Salberg G.,
Moe L.,
Larsen R. H.
Publication year - 2005
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/j.1476-5810.2005.064an.x
Subject(s) - liposome , spleen , biodistribution , medicine , distribution (mathematics) , doxorubicin , osteosarcoma , cancer , cancer research , pharmacology , pathology , chemistry , chemotherapy , in vitro , biochemistry , mathematical analysis , mathematics
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 emitter 223 Ra, encapsulated in doxorubicin‐containing‐liposomes (Caelyx ® /Doxil ® ). Methods: Caelyx ® was given before the injection of liposomal 223 Ra 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. Results: 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 t 1/2 was ∼28 h (BalbC mice) and in the dog t 1/2 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. Conclusions: Liposomal 223 Ra 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.