Radiation improves the distribution and uptake of liposomal @entity632 (caelyx) in XXXX @entity421 xenografts.

@entity1 @entity632 @entity137 @entity851 @entity5 @entity19 @entity519 @entity421 @entity422
Liposomal drug delivery appears to improve the antitumor effect and reduce @entity137 compared with the free drug. The therapeutic index may be improved further by combining cytotoxic drugs and radiotherapy. Successful therapy requires that the cytotoxic agents reach the @entity5 cells. Therefore, we studied @entity5 growth and the microdistribution of liposomal @entity632 (Caelyx) with and without additional ionizing radiation in @entity1 @entity421 xenografts in athymic @entity19 . Caelyx was injected i.v. 1 day before single or fractionated radiotherapy. Both chemoirradiation regimens induced significant @entity851 and worked synergistically. Confocal laser scanning microscopy showed that intact liposomes were located in close proximity to endothelial cells, and the distribution of released @entity632 was heterogeneous. Before radiotherapy, hardly any @entity632 was localized in the central parts of the @entity5 . Radiotherapy increased the @entity5 uptake of @entity632 by a factor of two to four, with drug being redistributed farther from the vessels in the @entity5 periphery and located around vessels in the central parts of the @entity5 . Colocalization of @entity632 and @entity519 cells showed no distribution of drug into @entity519 areas. Dynamic contrast-enhanced @entity422 day before the injection of Caelyx and 2 days after treatment start showed that the combined treatment reduced the vascular volume and the vascular transfer rate of the MRI tracer. The results show that chemoirradiation with Caelyx induces synergistic treatment effects. Improved intratumoral drug uptake and distribution are responsible to some extent for the enhanced antitumor effect.
