title: Molecular imaging of fibrosis using a novel collagen-binding peptide labelled with99mTc 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 (Kd= 861 nM) and (GPO)9(Kd= 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 coupling99mTc. Labelling efficiency of99mTc-CBP1495 was 95.06 ± 1.08 %. The physico-chemical properties, tracer kinetics and biodistribution of99mTc-CBP1495 were carried out, and showed that the peptide stably chelated99mTc in vitro and in vivo. SPECT/CT imaging with99mTc-CBP1495 was performed in rat fibrosis models, and revealed that99mTc-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 that99mTc-CBP1495 uptake was positvely correlated with Hyp content in lungs (P < 0.0001, r2= 0.8266) or livers (P < 0.0001, r2= 0.7581). Therefore, CBP1495 is a novel collagen-binding peptide, and99mTc-labelled CBP1495 may be a promising radiotracer for the molecular imaging of fibrosis.
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.|Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Ding
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Kaiyun
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Shibin
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Qianwei
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China. swhuangdde@163.com.
authors.forename: Dingde
authors.identifier: 0000-0002-1354-3878
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. shimingyang@yahoo.com.
authors.forename: Shiming
authors.initials: S
authors.lastname: Yang
mesh_terms: D000818:Animals; D001761:Bleomycin; D002251:Carbon Tetrachloride; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006909:Hydroxyproline / Q000737:chemistry / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D011485:Protein Binding; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D013194:Staining and Labeling / Q000379:methods; D013667:Technetium / Q000737:chemistry* / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D024042:Collagen Type I; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D012795:Sialoglycoproteins; C571744:bone sialoprotein (35-62), human; D001761:Bleomycin; D013667:Technetium; D002251:Carbon Tetrachloride; D006909:Hydroxyproline
keywords: Collagen-binding peptide; Fibrosis; Molecular imaging; Radionuclide imaging; Single-photon emission-computed tomography