Recombinant versus natural human 111In-β2-microglobulin for scintigraphic detection of Aβ2m amyloid in dialysis patients

Abstract

Background. We previously introduced scintigraphy with 131I-labeled β2-microglobulin (β2m), purified from uremic hemofiltrate, that is, 'natural' β2m, to specifically detect β2m-associated amyloidosis (Aβ2m) in hemodialysis (HD) patients. Methods. To improve the safety and resolution of the scan, we covalently bound the chelator diethylenetriaminepentaacetic acid to natural β2m to allow radiolabeling with 111In. In a second step, we generated and evaluated the usage of recombinant human β2m (rhβ2m) for scintigraphy. Results. Using natural 111In-labeled β2m, eight patients on HD for 0 to 17 years, without evidence of Aβ2m, were scanned. Whole-body scintigraphy at 48 to 72 hours postinjection revealed no significant tracer accumulation over joint regions. In contrast, nine patients on HD for 10 to 21 years with clinical, radiological, or histologic (N = 4) evidence of Aβ2m showed selective tracer uptake over various joint regions. Tracer accumulation in visceral organs, which could not be related to tracer elimination or metabolism, was not detected. Compared with the previous 131I β2m scan, scintigraphy with 111In-labeled β2m offered highly improved image contrast, increased sensitivity, and a 50 to 70% reduction of the radiation exposure. Scanning with 111In-labeled recombinant human β2m was performed in six patients: No significant tracer accumulation was observed over joint regions in two patients on short-term HD without evidence of Aβ2m; in contrast, local tracer accumulations similar to those observed with natural β2m could be demonstrated in four long-term (10 to 27 years) HD patients with clinical, radiological, and histologic (N = 1) evidence of Aβ2m. Conclusion. Scintigraphy for Aβ2m with 111In-labeled rhβ2m provides a homogenous and safe recombinant protein source and leads to enhanced sensitivity and lower radiation exposure.