Poster Sessions

CANCER-13

Hemant Sarin

H. Sarin, A. Kanevsky, H. Wu, A. Sousa, C. Wilson, M. Aronova, G. Griffiths, R. Leapman, H. Vo

Physiologic Upper Limit of Pore Size in the Blood-Tumor Barrier of Malignant Solid Tumors

The blood-tumor barrier of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. In this study, we probed in vivo the physiologic upper limit of pore size within the blood-tumor barrier of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site. The blood and tumor tissue pharmacokinetics of intravenously administered Gd-DTPA conjugated PAMAM dendrimer generations (G) 5 through 8 were visualized in vivo over 600 to 700 minutes by dynamic contrast-enhanced MRI. The respective Gd-dendrimer generations were visualized in vitro by annular dark field STEM. The estimated diameters of Gd-G7 dendrimers were 11 ± 1 nm and those of Gd-G8 dendrimers were 13 ± 1 nm. The physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumor microvasculature is approximately 12 nm independent of host site. The higher permeability of the blood-tumor barrier of malignant peripheral tumors to macromolecules smaller than approximately 12 nm in diameter is attributable to the presence of a greater number of pores underlying the glycocalyx of the blood-tumor barrier of malignant peripheral tumor microvasculature.