Scintigraphic methods to detect β2‐microglobulin associated amyloidosis (Aβ2‐microglobulin amyloidosis)

β2-Microglobulin-derived amyloidosis (Aβ2m) represents a major cause or morbidity in patients with end-stage renal disease. Symptoms of Aβ2m 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 Aβ2m-precursor protein, β2-microglobulin (β2m), yield more specific information. Using 123 I-labelled SAP, Aβ2m 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 Aβ2m deposits. Scanning with 131 I-labelled β2m, in contrast, yielded tracer accumulations corresponding to the typical distribution pattern of Aβ2m. 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 β2m (rhβ2m). 111 In-rhβ2m again failed to show significant tracer accumulation over joint regions in patients on short-term HD without evidence of Aβ2m amyloidosis. In contrast, local tracer accumulations similar to those observed with natural, 111 In-labelled β2m could be demonstrated in long-term HD patients with evidence of Aβ2m amyloidosis. In conclusion, scintigraphy for Aβ2m with 111 In-labelled rhβ2m provides a homogenous and safe recombinant protein source, and allows for the sensitive and specific non-invasive detection of Aβ2m-amyloid deposits in dialysis patients.