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Research Article
Rapid fluorescence imaging of human hepatocellular carcinoma using the β-galactosidase-activatable fluorescence probe SPiDER-βGal
Hidemasa Kubo
Kyoto Prefectural University of Medicine
Corresponding Author
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Fluorescence imaging of tumours facilitates rapid intraoperative diagnosis. Thus far, a promising activatable fluorescent probe for hepatocellular carcinoma (HCC) has not been developed. Herein, the utility of the fluorescence imaging of HCC using a β-galactosidase (β-Gal)-activatable fluorescence probe SPiDER-βGal was examined. β-Gal activity was measured in cryopreserved tissues from 68 patients. Live cell imaging of HCC cell lines and imaging of tumour-bearing model mice were performed using SPiDER-βGal. Furthermore, fluorescence imaging was performed in 27 freshly resected human HCC specimens. In cryopreserved samples, β-Gal activity was significantly higher in tumour tissues than in non-tumour tissues. Fluorescence was observed in HCC cell lines. In mouse models, tumours displayed stronger fluorescence than normal liver tissue. In freshly resected specimens, fluorescence intensity in the tumour was significantly higher than that in non-tumour liver specimens as early as 2 min after spraying. Receiver operating characteristic curves were generated to determine the diagnostic value of SPiDER-βGal 10 min after its spraying; an area under the curve of 0.864, sensitivity of 85.2%, and specificity of 74.1% were observed for SPiDER-βGal. SPiDER-βGal is useful for the rapid fluorescence imaging of HCC. Fluorescence imaging guided by SPiDER-βGal would help surgeons detect tumors rapidly and achieve complete liver resection.
Keywords
fluorescence imaging, β-galactosidase, fluorescence probe, hepatocellular carcinoma, human specimen
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Rapid fluorescence imaging of human hepatocellular carcinoma using the β-galactosidase-activatable fluorescence probe SPiDER-βGal
Hidemasa Kubo
Kyoto Prefectural University of Medicine
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 21 Jan, 2021
No community comments so far
Reviewers invited
Invitations sent on 03 Feb, 2021
Editor assigned
On 03 Feb, 2021
Editor invited
On 20 Jan, 2021
Submission checks complete
On 19 Jan, 2021
First submitted
On 15 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Fluorescence imaging of tumours facilitates rapid intraoperative diagnosis. Thus far, a promising activatable fluorescent probe for hepatocellular carcinoma (HCC) has not been developed. Herein, the utility of the fluorescence imaging of HCC using a β-galactosidase (β-Gal)-activatable fluorescence probe SPiDER-βGal was examined. β-Gal activity was measured in cryopreserved tissues from 68 patients. Live cell imaging of HCC cell lines and imaging of tumour-bearing model mice were performed using SPiDER-βGal. Furthermore, fluorescence imaging was performed in 27 freshly resected human HCC specimens. In cryopreserved samples, β-Gal activity was significantly higher in tumour tissues than in non-tumour tissues. Fluorescence was observed in HCC cell lines. In mouse models, tumours displayed stronger fluorescence than normal liver tissue. In freshly resected specimens, fluorescence intensity in the tumour was significantly higher than that in non-tumour liver specimens as early as 2 min after spraying. Receiver operating characteristic curves were generated to determine the diagnostic value of SPiDER-βGal 10 min after its spraying; an area under the curve of 0.864, sensitivity of 85.2%, and specificity of 74.1% were observed for SPiDER-βGal. SPiDER-βGal is useful for the rapid fluorescence imaging of HCC. Fluorescence imaging guided by SPiDER-βGal would help surgeons detect tumors rapidly and achieve complete liver resection.
Figure 1
Figure 2
Figure 3
Figure 4