Monoclonal antibodies to amyloid subunit proteins for in vivo radioimmunodetection of amyloid diseases

Amyloid fibrils of systemic amyloidosis are low molecular weight subunit proteins with poor immunogenicity and a tendency to polymerize. Antibodies to these proteins are useful for the detection of amyloid deposits in-situ. The extracellular location of amyloid deposits and proximity to congophilic angiopathy suggest the potential of labeled monocional antibodies (MAb) for in vivo radioimmunodetection. The authors tested feasibility of this approach using two rat MAbs to mouse AA protein in casein-induced amyloidosis, a model system for human secondary amyloidosis. The antibodies were labeled with I-125, I-123, and In-111 with good specificity retention. Amyloidotic mice were pretreated with 50 ..mu..g colchicine ip 3 hr before receiving radioiodinated MAb via the tall vein. Controls included injection of MAb to normal mice and of labeled polyclonal normal rat IgG (pIg) into amyloidotic and control mice. Blood clearance of MAb was faster in amyloidotic than control groups. Fractionation studies showed that both MAb and pIg were uncomplexed. Studies up to 96 hr showed specific and high uptake at sites of amyloid deposition (saline perfused liver, spleen, kidney. Specific localization was confirmed by whole body autoradiography (I-125, 20 ..mu..Ci/animal; 50 ..mu..g MAb) and by external imaging (I-123, 200 ..mu..Ci/animal, 10-15 ..mu..g MAb) of amyloidoticmore » mice studied at 4-72 hr. Amyloidotic animals showed perifollicular localization in spleen, periportal in liver, and glomerular in kidney; scans of controls showed diffuse early washout. These results document the feasibility of using MAbs to fibril subunit proteins for the in vivo detection and therapy of amyloidosis.« less