Scintigraphic methods to detect beta2-microglobulin associated amyloidosis (Abeta2-microglobulin amyloidosis)

Abstract

beta2-Microglobulin-derived amyloidosis (Abeta2m) represents a major cause or morbidity in patients with end-stage renal disease. Symptoms of Abeta2m amyloid are mainly related to (peri-) articular amyloid deposition. Conventional non-invasive diagnostic techniques, i.e. clinical evaluation, joint ultrasonography or X-ray, computed tomography or magnetic resonance imaging findings, as well as conventional bone scans, suffer from relative non-specificity and/or low sensitivity. Two recent methods, namely scintigraphy with radiolabelled serum amyloid P component (SAP) or with the radiolabelled Abeta2m-precursor protein, beta2-microglobulin (beta2m), yield more specific information. Using (123)I-labelled SAP, Abeta2m deposits have been visualized in several long-term haemodialysis (HD) patients. However, this scan did not show tracer accumulation in other frequently involved sites, such as hips or shoulders, but did frequently label the spleen, which is usually spared from Abeta2m deposits. Scanning with (131)I-labelled beta2m, in contrast, yielded tracer accumulations corresponding to the typical distribution pattern of Abeta2m. Specificity of this method was shown by several methods, and the sensitivity was found to markedly exceed that of combined clinical and radiological investigations. Recently, both the radiation exposure and the optical resolution of this latter scan have been further refined by substituting (131)I with (111)In. In a final step we generated recombinant human beta2m (rhbeta2m). (111)In-rhbeta2m again failed to show significant tracer accumulation over joint regions in patients on short-term HD without evidence of Abeta2m amyloidosis. In contrast, local tracer accumulations similar to those observed with natural, (111)In-labelled beta2m could be demonstrated in long-term HD patients with evidence of Abeta2m amyloidosis. In conclusion, scintigraphy for Abeta2m with (111)In-labelled rhbeta2m provides a homogenous and safe recombinant protein source, and allows for the sensitive and specific non-invasive detection of Abeta2m-amyloid deposits in dialysis patients.