[Anionic long circulation liposomes mediated antisense scintigraphy in tumor-bearing rats]

This paper was aimed to investigate the biodistribution and ability of free 131-bcl-2/bcl-xl ASON (FA) and anionic long circulation liposomes encapsulated with 131I-bcl-2/bcl-xlASON (NA), in tumor-bearing rats, to image breast cancer. We investigated the tissue distribution of NA in virgin female Sprague-Dawley (SD) rats with n-methyl nitrosourea (MNU)-induced breast cancers in situ. The percentage of the injected dose per gram (%ID/g) was calculated, with the maximum ratios of tumor to blood and tumor to muscle, after injections of NA and FA for 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 12 h and 24 h, respectively. The ability of NA to image breast cancer in tumor-bearing rats was determined using emission computed tomography (ECT). Seventy percent (90/130) SD rats in the study developed mammary tumors after MNU injection with the average latency (NA) (96 +/- 1.2)days. The %ID/g of NA in breast cancer tissue, tumor bearing rats in liver and spleen tumor tissues after 10 hours were (6.23 +/- 0.23) %ID/g, (12.00 +/- 0.26) %ID/g and (18.25 +/- 1.33)% ID/g, respectively. The ratios of tumor to blood 6.29 +/- 0.76 and tumor to muscle 10.55 +/- 0.68 in tumor bearing rats slowly maximized at 10 h post injection of NA, most probably due to the enhanced permeability and retention effect. Hence in radionuclide antisense scintigraphy, the breast cancer in rat was clearly displayed at 10h after iv administration of NA-D. However, tumors were not visualized in rats with the iv injection of NS and NN even at the delayed time. Due to the inhibition of rapid uptake of NA by the reticulo-endothelial system, NA displays valuable pharmacologic properties characterized by the enhanced accumulation in tumor.