Small-animal SPECT/CT imaging of cancer xenografts and pulmonary fibrosis using a <sup>99m</sup>Tc-labeled integrin αvβ6-targeting cyclic peptide with improved <em>in vivo</em> stability

Hao Liu; Liquan Gao; Xinhe Yu; Lijun Zhong; Jiyun Shi; Bing Jia; Nan Li; Zhaofei Liu; Fan Wang

doi:10.1007/s41048-018-0071-1

Volume 4 Issue 5

Nov. 2018

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Article Navigation > Biophysics Reports > 2018 > 4(5): 254-264

Hao Liu, Liquan Gao, Xinhe Yu, Lijun Zhong, Jiyun Shi, Bing Jia, Nan Li, Zhaofei Liu, Fan Wang. Small-animal SPECT/CT imaging of cancer xenografts and pulmonary fibrosis using a 99mTc-labeled integrin αvβ6-targeting cyclic peptide with improved in vivo stability[J]. Biophysics Reports, 2018, 4(5): 254-264. doi: 10.1007/s41048-018-0071-1

Citation:

Hao Liu, Liquan Gao, Xinhe Yu, Lijun Zhong, Jiyun Shi, Bing Jia, Nan Li, Zhaofei Liu, Fan Wang. Small-animal SPECT/CT imaging of cancer xenografts and pulmonary fibrosis using a ^99mTc-labeled integrin αvβ6-targeting cyclic peptide with improved in vivo stability[J]. Biophysics Reports, 2018, 4(5): 254-264. doi: 10.1007/s41048-018-0071-1

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Small-animal SPECT/CT imaging of cancer xenografts and pulmonary fibrosis using a ^99mTc-labeled integrin αvβ6-targeting cyclic peptide with improved in vivo stability

doi: 10.1007/s41048-018-0071-1

Hao Liu¹,
Liquan Gao¹,
Xinhe Yu¹,
Lijun Zhong²,
Jiyun Shi³,
Bing Jia^1,2,
Nan Li⁴,
Zhaofei Liu^{1
,
,},
Fan Wang^{1,3
,}

1 Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
2 Medical and Healthy Analytical Center, Peking University, Beijing 100191, China
3 Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
4 Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China

Funds: This work was partially supported by the National Key R&D Program of China (2018YFC1313300 and 2017YFA0205600), the National Natural Science Foundation of China (81471712, 81671747, 81630045, 81873907, and 81420108019), the Beijing Natural Science Foundation (L172007), the Beijing Nova Program Interdisciplinary Cooperation Project (Z181100006218136), and the Clinical Medicine Plus X-Young Scholars Project of Peking University (PKU2018LCXQ017).

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Corresponding author: Zhaofei Liu, Fan Wang
Received Date: 24 May 2018
Publish Date: 02 November 2018

Abstract

Abstract

Integrin αvβ6 is expressed at an undetectable level in normal tissues, but is remarkably upregulated during many pathological processes, especially in cancer and fibrosis. Noninvasive imaging of integrin αvβ6 expression using a radiotracer with favorable in vivo pharmacokinetics would facilitate disease diagnosis and therapy monitoring. Through disulfide-cyclized method, we synthesized in this study, a new integrin αvβ6-targeted cyclic peptide (denoted as cHK), and radiolabeled it with ^99mTc. The ability of the resulting radiotracer ^99mTc-HYNIC-cHK to detect integrin αvβ6 expression in pancreatic cancer xenografts and idiopathic pulmonary fibrosis was evaluated using small-animal single-photon emission computed tomography (SPECT)/computed tomography (CT). ^99mTc-HYNIC-cHK showed significantly improved in vivo metabolic stability compared to the linear peptide-based radiotracer ^99mTc-HYNIC-HK. ^99mTc-HYNIC-cHK exhibited similar biodistribution properties to ^99mTc-HYNIC-HK, but the tumorto-muscle ratio was significantly increased (2.99±0.87 vs. 1.82±0.27, P<0.05). High-contrast images of integrin αvβ6-positive tumors and bleomycin-induced fibrotic lungs were obtained by SPECT/CT imaging using ^99mTc-HYNIC-cHK. Overall, our studies demonstrate that ^99mTc-HYNIC-cHK is a promising SPECT radiotracer for the noninvasive imaging of integrin αvβ6 in living subjects.
- Integrin αvβ6,
- Pancreatic cancer,
- Pulmonary fibrosis,
- Molecular imaging,
- Peptide cyclization,
- Singlephoton emission computed tomography (SPECT)

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References(57)

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