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

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• 作者：Lei Zheng ; Xiaojiang Ding ; Kaiyun Liu ; Shibin Feng ; Bo Tang ; Qianwei Li…
• 关键词：Collagen ; binding peptide ; Fibrosis ; Molecular imaging ; Radionuclide imaging ; Single ; photon emission ; computed tomography
• 刊名：Amino Acids
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：49
• 期：1
• 页码：89-101
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biochemistry, general; Analytical Chemistry; Biochemical Engineering; Life Sciences, general; Proteomics; Neurobiology;
• 出版者：Springer Vienna
• ISSN：1438-2199
• 卷排序：49

文摘

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, r2 = 0.8266) or livers (P < 0.0001, r2 = 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.