TY - JOUR
T1 - A collagen-binding protein enables molecular imaging of kidney fibrosis in vivo
AU - Baues, M.
AU - Klinkhammer, B.M.
AU - Ehling, J.
AU - Gremse, F.
AU - van Zandvoort, M.A.M.J.
AU - Reutelingsperger, C.P.M.
AU - Daniel, C.
AU - Amann, K.
AU - Babickova, J.
AU - Kiessling, F.
AU - Floege, J.
AU - Lammers, T.
AU - Boor, P.
N1 - Funding Information:
This study was supported by the German Research Foundation (DFG: SFB/TRR57, SFB/TRR219, SFB1066, BO3755/3-1, BO3755/6-1, GR5027/2-1, and RTG2375), the German Ministry of Education and Research (BMBF: STOP-FSGS- 01GM1901A), the European Research Council (ERC: StG-309495 and PoC-813086), the European Union (EU-EFRE: European Fund for Regional Development: I3-STM 0800387), the Interdisciplinary Centre for Clinical Research at RWTH (IZKF K7-3, E7-6, and O3-2), and the RWTH START program (09/15, 124/14, and 152/12).
Publisher Copyright:
© 2019 International Society of Nephrology
PY - 2020/3/1
Y1 - 2020/3/1
N2 - d 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.
AB - d 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.
KW - chronic kidney disease (ckd)
KW - collagen
KW - extracellular matrix
KW - molecular imaging
KW - non-invasive imaging
KW - progenitors
KW - renal fibrosis
KW - PROGENITORS
KW - chronic kidney disease (CKD)
U2 - 10.1016/j.kint.2019.08.029
DO - 10.1016/j.kint.2019.08.029
M3 - Article
C2 - 31784048
SN - 0085-2538
VL - 97
SP - 609
EP - 614
JO - Kidney International
JF - Kidney International
IS - 3
ER -