RAGE VC1 binds preferentially to systemic AA amyloid in vivo. Contrast enhanced SPECT/CT imaging at 2 h post-injection of 125I-RAGE VC1 in representative mice with systemic AA (A–D) and dual-energy SPECT/CT images of 125I-RAGE VC1 and 99mTc-p5 in a representative single mouse with AA (E & F). Radiolabeled 125I-RAGE (red) was observed in amyloid-laden liver (L) and spleen (S) of mice, with free radioiodide in the thyroid (T) and stomach (St). Three-dimensional image views (D) confirmed the hepatosplenic uptake of 125I-RAGE VC1. The distribution of 125I-RAGE VC1 in AA mice was consistent with that of the amyloid-reactive peptide 99mTc-p5 in AA mice (E–F). Image views: A, axial; B, E and F, coronal; C, sagittal; and D, 3D representation.