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

Imaging in the Dialysis Patient: Nuclear Medicine Studies in the Dialysis Patient

“…Both substances show a specific enrichment in amyloid tissue and have been proven to be more sensitive than other noninvasive techniques in the diagnosis of Ab 2 M amyloidosis, even in asymptomatic patients, and can be used for monitoring disease progress (46,47,49,50). The most advanced step in imaging amyloidosis in dialysis patients is the use of 111 In-labeled recombinant human b 2 M (rhb 2 M), which allows the sensitive and specific noninvasive detection of b 2 M amyloidosis with a relatively low radioactive burden and good image quality (46,47). If direct scintigraphic imaging of Ab 2 M amyloidosis becomes more widely available, it could be used as an efficient tracer in monitoring therapeutic regimens in dialysis patients with amyloidosis.…”

“…The “gold standard” for diagnosis is considered to be histologic confirmation of β 2 M amyloid; however, biopsy is seldom performed. The radionuclide bone scan in Aβ 2 M amyloidosis is neither specific nor very sensitive (47). Imaging with gallium 67 citrate or Tl‐201 chloride has been reported to be accurate in evaluating the activity and response to therapy of such lesions (48).…”

“…Two scintigraphic methods, the radioiodinated serum amyloid P component (SAP) and the Aβ 2 M precursor protein, β 2 ‐microglobulin (β 2 M), labeled with 123 I/ 131 I or 111 In have gained interest within the last years (46,47,49,50). Both substances show a specific enrichment in amyloid tissue and have been proven to be more sensitive than other noninvasive techniques in the diagnosis of Aβ 2 M amyloidosis, even in asymptomatic patients, and can be used for monitoring disease progress (46,47,49,50).…”

Rapid Progression of Destructive Spondyloarthropathy

“…It has been recently shown that scintigraphy in which the radioactive tracer (iodine 131 or indium 111) is labeled to the amyloid precursor protein ␤ 2 -microglobulin is superior to MRI in demonstrating deposition of ␤ 2 -microglobulin amyloid in dialysis patients. 13,14 This is particularly so when recombinant human ␤ 2 -microglobulin is used as the labeling agent. 14…”

Nuclear imaging of amyloidosis

“…The radiotracer is accumulated directly in amyloid deposits [32]. A disadvantage of 131 I-labeled radiotracer was poor spatial resolution, which made imaging of small joints problematic and increased the radiation dose due to unnecessary β(−) radiation [34]. In 2000, Schaeffer combined β2M with gamma emitter 111 In [35].…”