Pathological deposition of
collagen is a hallmark of kidney
fibrosis. To illustrate this process we employed multimodal optical imaging to visualize and quantify
collagen deposition in murine models of kidney
fibrosis (
ischemia-reperfusion or unilateral
ureteral obstruction) using the
collagen-binding adhesion
protein CNA35. For in vivo imaging, we used hybrid computed tomography-fluorescence molecular tomography and CNA35 labeled with the near-infrared fluorophore Cy7. Upon
intravenous injection, CNA35-Cy7 accumulation was significantly higher in fibrotic compared to non-fibrotic kidneys. This difference was not detected for a non-specific scrambled version of CNA35-Cy7. Ex vivo, on kidney sections of mice and patients with renal
fibrosis, CNA35-FITC co-localized with fibrotic
collagen type I and III, but not with the basement membrane
collagen type IV. Following
intravenous injection, CNA35-FITC bound to both interstitial and perivascular fibrotic areas. In line with this perivascular accumulation, we observed significant perivascular
fibrosis in the mouse models and in biopsy sections from patients with
chronic kidney disease using computer-based morphometry quantification. Thus, molecular imaging of
collagen using CNA35 enabled specific non-invasive quantification of kidney
fibrosis.
Collagen imaging revealed significant perivascular
fibrosis as a consistent component next to the more commonly assessed interstitial
fibrosis. Our results lay the basis for further probe and protocol optimization towards the clinical translation of molecular imaging of kidney
fibrosis.