TUMOR-CELL ENDOCYTOSIS IMAGING FACILITATES DELINEATION OF THE GLIOMA-BRAIN INTERFACE

We describe a method for measuring tumor cell endocytosis in vivo and provide the anatomic correlate of this tumor cell function using a sup erparamagnetic and histologically detectable marker for cell uptake (M ION). Rats (n = 22) were intrahemispherically implanted with a thymidi ne kinase (TK)-positive 9L gliosarcoma cell line, where TK served as t he tumor marker. Twenty-four hours after intravenous injection of 10 m g Fe/kg of MION, rat brains were removed and underwent MR imaging ex v ivo at near-microscopic resolution (isotropic voxel size of 86 mu m, 9 .4 T) prior to histologic processing. The imaging probe accumulated wi thin tumor cells adjacent to the hyperpermeable tumor-brain interface including microscopic deposits and along finger-like invasions of the tumor into brain, facilitating the demarcation of the true histologic tumor border in three dimensions by MR microscopy. The method has pote ntial research and clinical implications for delineating the tumor-bra in interface prior to therapy and/or for providing a rational basis fo r imaging nanocolloid drug delivery to solid tumors. (C) 1997 Academic Press