LABELING OF CEREBRAL AMYLOID IN-VIVO WITH A MONOCLONAL-ANTIBODY

We assessed the ability of a murine monoclonal antibody to bind select ively to beta-amyloid in the brains of living nonhuman primates. To ci rcumvent the blood-brain barrier, we injected unlabeled antibody 10D5 (murine whole IgG(1) and/or Fab fragments) into the cerebrospinal flui d of the cisterna magna in three aged monkeys. A control animal was gi ven an intracisternal injection of nonimmune mouse whole IgG plus Fab. Twenty-four hours later, the animals were perfused and prepared for i mmunohistochemical detection of bound murine immunoglobulin in brain. All three experimental animals showed selective binding of 10D5 to app roximately 5-15% of amyloid deposits in cerebral cortex, primarily nea r the cortical surface. There was no labeling in the control animal. I n vivo-labeled deposits were confirmed to be beta-amyloid by electron microscopy and by in vitro immunohistochemistry in adjacent sections. The animals tolerated the injection well, although some polymorphonucl ear leukocytes infiltrated portions of the subarachnoid space and supe rficial neocortex. These results provide the first demonstration that it may be feasible to selectively direct a tagged monoclonal antibody to beta-amyloid in the brain for therapeutic or diagnostic purposes. W ith enhancement of labeling efficiency, the method also may be useful for studying the progression of beta-amyloidosis in experimental anima ls using emission tomography.