Scintigraphic methods to detect beta 2-microglobulin associated amyloidosis (A beta 2-microglobulin amyloidosis)

beta2-Microglobulin-derived amyloidosis (A beta 2m) represents a major caus e or morbidity in patients with end-stage renal disease. Symptoms of A beta 2m amyloid are mainly related to (peri-) articular amyloid deposition. Con ventional non-invasive diagnostic techniques, i.e. clinical evaluation, joi nt ultrasonography or X-ray, computed tomography or magnetic resonance imag ing 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 radiolabell ed A beta 2m-precursor protein, beta2-microglobulin (beta 2m), yield more s pecific information. Using I-123-labelled SAP, A beta 2m 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 us ually spared from A beta 2m deposits. Scanning with I-131-labelled beta 2m, in contrast, yielded tracer accumulations corresponding to the typical dis tribution pattern of A beta 2m. Specificity of this method was shown by sev eral methods, and the sensitivity was found to markedly exceed that of comb ined clinical and radiological investigations. Recently, both the radiation exposure and the optical resolution of this latter scan have been further refined by substituting I-131 with In-111. In a final step we generated rec ombinant human beta 2m (rh beta 2m) In-111-rh beta 2m again failed to show significant tracer accumulation over joint regions in patients on short-ter m HD without evidence of A beta 2m amyloidosis. In contrast, local tracer a ccumulations similar to those observed with natural, In-111-labelled beta 2 m could be demonstrated in long-term HD patients with evidence of A beta 2m amyloidosis. In conclusion, scintigraphy for A beta 2m with In-111-labelle d rh beta 2m provides a homogenous and safe recombinant protein source, and allows for the sensitive and specific non-invasive detection of A beta 2m- amyloid deposits in dialysis patients.