Permeability of human brain tumor to 99mTc-gluco-heptonate and 99mTc-albumin. Implications for monoclonal antibody therapy.

Abstract

The variable penetration of chemotherapeutic drugs into brain and tumor is more dependent upon lipid solubility than upon size. In contrast, the molecular weight of virus- and tumor-specific monoclonal antibodies appears to limit uptake. The authors have studied eight patients with malignant brain tumors in order to compare tumor uptake of an iodinated contrast agent evaluated by computerized tomography scanning with uptake of the low and high molecular weight imaging agents technetium-99m (99mTc)-glucoheptonate and 99mTc-albumin, respectively, measured by radionuclide brain scanning. The agent 99mTc-labeled albumin was chosen for evaluation because its molecular weight (68,000) is similar to that of the most clinically promising monoclonal antibody fragment, the immunoglobulin (Ig) G Fab monomeric fragment. The radionuclide brain scans in the eight patients showed highly variable permeability of brain tumor to these markers, with uptake of the high molecular weight marker in the tumor being much less than that of the low molecular weight radionuclide. A clinical implication of these studies is that the success of monoclonal antibody therapy in the treatment of malignant brain tumors may require techniques to increase permeability of the blood-brain barrier and blood-tumor barrier to protein.