Simultaneous measurements of blood flow and blood-to-tissue transport in xenotransplanted medulloblastomas

Abstract

We used double-label quantitative autoradiography to study blood flow (with [131I]iodoantipyrine) and blood-to-tissue transport (with [14C]-alpha-aminoisobutyric acid) in 20 TE-671 medulloblastomas xenotransplanted into nude rats. Microscopically, two distinct patterns of tumor growth were observed: (a) a solid tumor mass; and (b) a tumor in which nearly all tumor cells were located perivascularly. These two tumor patterns differed markedly in values of blood flow (F) and the transfer constant (K) of alpha-aminoisobutyric acid. The solid tumors (N = 17) had averaged mean values of F = 36.8 +/- 5.3 (SE) and K = 8.0 +/- 0.7 ml/100 g/min. The perivascular tumors, which were fewer in number (N = 3), had averaged mean values of F = 83.8 +/- 9.8 and K = 0.4 +/- 0.06 ml/100 g/min. Calculated values of the net extraction fraction (En) of alpha-aminoisobutyric acid were 0.54 +/- 0.07 for the solid tumors and 0.009 +/- 0.001 for the perivascular tumors. K and En for the solid tumors are the highest for any brain tumor model reported to date. The high rates of blood-to-tissue transport may explain why intracranial TE-671 medulloblastomas in nude mice respond to treatment with water-soluble chemotherapeutic drugs, unlike most other brain tumor models.