Fig. 3.

ASARM-induced Gd³⁺ release from Omniscan is prevented by SPR4 peptide and increases GBCA stability in renal MRI scans of Hyp mice ex vivo (n = 6). A: MRI (ex vivo) of representative kidneys resected 2 h after intraperitoneal injection with Omniscan (Gd-OMN) or Gd-OMN+SPR4 peptide as indicated in the scheme. Photo A: wild-type mouse (WT). Photos B and C: Hyp mice (Hyp mice overexpress ASARM peptides). Note in Hyp mice treated only with gadodiamide (photo B), the MRI signal is quenched compared with WT mice (photo A) and Hyp mice treated with Gd-OMN+SPR4 peptide (photo C). This indicates preferential desequestration and release of Gd³⁺ ion from the gadodiamide vehicle in Hyp mice due to excess ASARM peptides (photo B). This is prevented in Hyp mice pretreated with SPR4 peptide (compare photos B and C). Thus SPR4 peptide indirectly stabilizes Omniscan (gadodiamide) by binding to ASARM peptide. Note the contrast images for WT mice, Hyp mice, and Hyp+SPR4-treated mice were identical to Hyp mice treated with Gd-OMN. Thus the quenching of the contrast signal by Gd-OMN is quite marked. See the text for a more detailed description. B: model illustrating the proposed ASARM peptide-induced release of toxic Gd³⁺ from GBCA resulting in nephrogenic systemic fibrosis (NSF). SPR4 peptide may prevent this by binding to and neutralizing ASARM peptide. Note that free Gd³⁺ as well as inducing organ/tissue toxicity is also reported to displace Ca²⁺ and PO⁴⁺ from bone and alter expressions of FGF23 and parathyroid hormone. This results in hyperphosphatemia, hypercalcemia, and soft tissue calcification.