In vitro affinity of 99Tcm-labelled N2S2 conjugates of chrysamine G for amyloid deposits of systemic amyloidosis

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Abstract
To date, systemic amyloidosis is diagnosed histologically in vitro using Congo red staining or in vivo using iodine-123 serum amyloid P component (123I-SAP) scintigraphy. 99Tcm-labelled derivatives of chrysamine G (CG), a lipophilic analogue of Congo red, were synthesized as potential tracer agents for direct and quantitative scintigraphic evaluation of amyloid deposits. To determine the affinity of 99Tcm-MAMA-CG, 99Tcm-Me4MAMA-CG and 99Tcm-MAMA-CG diethyl ester for amyloid, in vitro autoradiography was performed on sections of human kidney biopsy cylinders from kidneys with amyloid deposits (types AA, Aλ and Aκ) or control kidney tissue after incubation with the respective tracer agents. The binding of 99Tcm-MAMA-CG and its tetramethyl derivative was higher to kidney biopsy material with amyloid deposits of the AA, Aλ or Aκ type compared with control kidney tissue. This higher binding was prevented by the presence of 10 μM Congo red in the incubation medium. The diethyl ester of 99Tcm-MAMA-CG did not demonstrate increased binding to Congo red-positive kidney tissue. In conclusion, 99Tcm-MAMA-CG and 99Tcm-Me4MAMA-CG localize specifically to amyloid deposits in human kidney tissue, suggesting that these tracer agents may be applicable as specific targeting agents for diagnostic purposes in clinical amyloidosis.