Molecular imaging of fibrosis using a novel collagen-binding peptide labelled with 99mTc on SPECT/CT.

Abstract

Fibrosis, closely related to chronic various diseases, is a pathological process characterised by the accumulation of collagen (largely collagen type I). Non-invasive methods are necessary for the diagnosis and follow-up of fibrosis. This study aimed to develop a collagen-targeted probe for the molecular imaging of fibrosis. We identified CPKESCNLFVLKD (CBP1495) as an original collagen-binding peptide using isothermal titration calorimetry and enzyme-linked immunosorbent assay. CBP1495 effectively bound to collagen type I (K d = 861 nM) and (GPO)9 (K d = 633 nM), a collagen mimetic peptide. Western blot and histochemistry validated CBP1495 targeting collagen in vitro and ex vivo. (Gly-(D)-Ala-Gly-Gly) was introduced to CBP1495 for coupling 99mTc. Labelling efficiency of 99mTc-CBP1495 was 95.06 ± 1.08 %. The physico-chemical properties, tracer kinetics and biodistribution of 99mTc-CBP1495 were carried out, and showed that the peptide stably chelated 99mTc in vitro and in vivo. SPECT/CT imaging with 99mTc-CBP1495 was performed in rat fibrosis models, and revealed that 99mTc-CBP1495 significantly accumulated in fibrotic lungs or livers of rats. Finally, 99mTc-CBP1495 uptake and hydroxyproline (Hyp), a specific amino acid of collagen, were quantitatively analysed. The results demonstrated that 99mTc-CBP1495 uptake was positvely correlated with Hyp content in lungs (P < 0.0001, r 2 = 0.8266) or livers (P < 0.0001, r 2 = 0.7581). Therefore, CBP1495 is a novel collagen-binding peptide, and 99mTc-labelled CBP1495 may be a promising radiotracer for the molecular imaging of fibrosis.

• Authors: Lei Zheng, Xiaojiang Ding, Kaiyun Liu, Shibin Feng, Bo Tang, Qianwei Li, Dingde Huang, Shiming Yang
• Journal: Amino acids (Amino Acids) Vol. 49 Issue 1 Pg. 89-101 (01 2017) ISSN: 1438-2199 [Electronic] Austria
• PMID: 27633720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• Peptide Fragments
• Radiopharmaceuticals
• Sialoglycoproteins
• bone sialoprotein (35-62), human
• Bleomycin
• Technetium
• Carbon Tetrachloride
• Hydroxyproline

Topics

• Animals
• Bleomycin
• Carbon Tetrachloride
• Collagen Type I (chemistry, metabolism)
• Female
• Hydroxyproline (chemistry, metabolism)
• Liver Cirrhosis (chemically induced, diagnostic imaging, metabolism)
• Male
• Mice
• Molecular Imaging (methods)
• Peptide Fragments (chemistry, metabolism, pharmacokinetics)
• Protein Binding
• Pulmonary Fibrosis (chemically induced, diagnostic imaging, metabolism)
• Rabbits
• Radiopharmaceuticals (chemistry, metabolism)
• Rats
• Rats, Sprague-Dawley
• Sialoglycoproteins (chemistry, metabolism, pharmacokinetics)
• Staining and Labeling (methods)
• Technetium (chemistry, metabolism)
• Tomography, Emission-Computed, Single-Photon