^99mTc-labelled immunoglobulin scintigraphy in arthritis: an analysis of synovial fluid activity

Abstract

The distribution of 99mTc-labelled human polyclonal non-specific immunoglobulin G (HIG) in the synovial fluid was studied in 14 patients with rheumatoid and non-rheumatoid arthritides. Analysis included the determination of the total activity per ml synovial fluid 6 h post-injection (p.i.) of the tracer as well as of the protein- and cell-bound fractions. At 6 h p.i., > 60% of the injected dose remained in plasma as protein-bound radioactivity. Values in the synovial fluid ranged between 0.001 and 0.009% of the injected dose per ml. Importantly, the synovial fluid to plasma ratio was consistently < 1 (range: 0.09-0.43), which is in the range of ratios observed for endogenous proteins in vivo. Similar values were obtained in samples of synovial tissue obtained at surgery in two patients. These data are consistent with the hypothesis that labelled HIG accumulates in the extracellular fluid (both within the synovial tissue and fluid) by non-specific mechanisms (such as increased blood pool and capillary permeability) and does not equilibrate with circulating plasma proteins in accordance with basic knowledge of synovial physiology. In addition, it was found that most of the activity remained bound to the proteins in the fluid and that cell-binding occurred to a very low degree that cannot be considered an important mechanism of uptake of this radiolabelled agent in vivo. These results provide the first evidence in an in vivo human setting that radiolabelled HIG accumulates mainly by non-specific mechanisms in inflamed joints.

99m-TECHNETIUM-LABELLED HUMAN IMMUNOGLOBULIN G SCINTIGRAPHY IN PERIPHERAL ENTEROPATHIC ARTHROPATHY

“…Specific or non-specific endocytosis of the protein by synoviocytes were considered as a potential mechanism of uptake 9, 13, 15, 24 but recent studies confirmed the lack of a significant role of cellular binding in determining the accumulation of 99m Tc-IgG in inflamed tissues. 9,16,17 The accumulation in sites of synovial inflammation seems to depend upon endothelial permeability, increased blood flow and probably increased immune response as stated by Jamar et al 16 In conclusion, our data indicate that 99m Tc-IgG scintigraphy can be appropriate for detecting inflammation of peripheral joints and can be used to establish the extent of arthritis in patients with inflammatory bowel disease. Further studies are needed to elucidate the specific mechanism behind the uptake in inflamed joints of patients with enteropathic arthropathies.…”

“…11-13, 15, 20, 22 In the previous studies 99m Tc-IgG scintigraphy was found to be 85% sensitive in detecting synovitis for histological findings and 65% sensitive in detecting clinical findings. 16,22 Berna et al 13 compared conventional bone scan and 99m Tc-IgG scintigraphy in 18 RA patients to assess the Fig. 3 The correlation between total tenderness and total 99m Tc-IgG scintigraphic scores ( p < 0.001, r = 0.79).…”

“…[10][11][12][13][14][15] Recent studies have shown that 99m Tc-IgG scintigraphy provide objective evidence for the presence of inflammatory joint activity in both rheumatoid arthritis and sero-negative spondyloarthropathies. 9,11,16,17 Its place in detection of enteropathic peripheral arthritis has not been evaluated.…”

Identification and evaluation of novel synovial tissue biomarkers in rheumatoid arthritis by laser scanning cytometry

“…For the last two decades, several studies have aimed to assess the degree of arthritis intensity with scintigraphic approaches. With techniques such as targeted immunoscintigraphy, the presence of relevant molecules can be highlighted by radiolabeled mAbs [4,19,20]. On the basis of the given amount of these relevant molecules involved in the pathophysiology of RA, it allows better staging of the disease and might provide a possibility to perform "evidence-based biologic therapy" for arthritis.…”

“…The scintigraphic detection of these radiolabeled mAbs allows direct visualization of the synovitis of RA. The combination of the assessment of disease-specific cellular biomarkers directly in the joint and noninvasive high-resolution in vivo imaging techniques, such as immunoscintigraphy or immuno-positron-emission tomography (PET), are suitable approaches to determine alterations in the joints and hence offer valuable tools for sensitive and specific diagnosis in RA [4-7]. …”