Integrin α6 targeted positron emission tomography imaging of hepatocellular carcinoma in mouse models

Guo Kai Feng, Jia Cong Ye, Wei Guang Zhang, Yan Mei, Chao Zhou, Yi Tai Xiao, Xin Ling Li, Wei Fan, Fan Wang, Mu Sheng Zeng

Research output: Contribution to journalArticle

Abstract

Integrin α6 emerges to be a diagnostic biomarker for hepatocellular carcinoma (HCC). Here, we translated our previously identified integrin α6 targeted peptide RWY into a positron emission tomography (PET) tracer 18F-RWY for the detection of HCC lesions in following four HCC mouse models including subcutaneous, orthotopic, genetically engineered and chemical induced HCC mice. 18F-RWY produced high PET signals in liver tumor tissues that were reduced by blocking studies using nonradiolabeled RWY peptide. We compared the integrin α6 targeted PET tracer 18F-RWY with the integrin αvβ3-targeted PET tracer 18F-3PRGD2 and the clinical PET tracer 18F-FDG in chemical induced HCC mice. Among 12 HCC identified by enhanced magnetic resonance imaging (MRI) with hepatocellular specific gadoxetate disodium Gd-EOB-DTPA, the sensitivities of 18F-RWY, 18F-3PRGD2 and 18F-FDG were approximately 92%, 73% and 50% while the tumor-to-liver ratios were 4.36 ± 1.41, 1.97 ± 0.43 and 1.63 ± 0.23 respectively. Additionally, PET imaging with the integrin α6 targeted 18F-RWY enabled to visualize small HCC lesions with diameters approximately 0.2 cm that was hard to be distinguished from surround hepatic vascular by enhanced MRI with Gd-EOB-DTPA. These findings potentiate the use of integrin α6 targeted PET tracer 18F-RWY for the detection of HCC.

Original languageEnglish (US)
Pages (from-to)11-21
Number of pages11
JournalJournal of Controlled Release
Volume310
DOIs
StatePublished - Sep 28 2019

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Integrins
Positron-Emission Tomography
Hepatocellular Carcinoma
Fluorodeoxyglucose F18
Liver
Magnetic Resonance Imaging
Peptides
Blood Vessels
Neoplasms
Biomarkers
gadolinium ethoxybenzyl DTPA

Keywords

  • Hepatocellular carcinoma
  • Integrin α6
  • Phage display
  • Positron emission tomography
  • Targeting peptide

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Integrin α6 targeted positron emission tomography imaging of hepatocellular carcinoma in mouse models. / Feng, Guo Kai; Ye, Jia Cong; Zhang, Wei Guang; Mei, Yan; Zhou, Chao; Xiao, Yi Tai; Li, Xin Ling; Fan, Wei; Wang, Fan; Zeng, Mu Sheng.

In: Journal of Controlled Release, Vol. 310, 28.09.2019, p. 11-21.

Research output: Contribution to journalArticle

Feng, Guo Kai ; Ye, Jia Cong ; Zhang, Wei Guang ; Mei, Yan ; Zhou, Chao ; Xiao, Yi Tai ; Li, Xin Ling ; Fan, Wei ; Wang, Fan ; Zeng, Mu Sheng. / Integrin α6 targeted positron emission tomography imaging of hepatocellular carcinoma in mouse models. In: Journal of Controlled Release. 2019 ; Vol. 310. pp. 11-21.
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abstract = "Integrin α6 emerges to be a diagnostic biomarker for hepatocellular carcinoma (HCC). Here, we translated our previously identified integrin α6 targeted peptide RWY into a positron emission tomography (PET) tracer 18F-RWY for the detection of HCC lesions in following four HCC mouse models including subcutaneous, orthotopic, genetically engineered and chemical induced HCC mice. 18F-RWY produced high PET signals in liver tumor tissues that were reduced by blocking studies using nonradiolabeled RWY peptide. We compared the integrin α6 targeted PET tracer 18F-RWY with the integrin αvβ3-targeted PET tracer 18F-3PRGD2 and the clinical PET tracer 18F-FDG in chemical induced HCC mice. Among 12 HCC identified by enhanced magnetic resonance imaging (MRI) with hepatocellular specific gadoxetate disodium Gd-EOB-DTPA, the sensitivities of 18F-RWY, 18F-3PRGD2 and 18F-FDG were approximately 92{\%}, 73{\%} and 50{\%} while the tumor-to-liver ratios were 4.36 ± 1.41, 1.97 ± 0.43 and 1.63 ± 0.23 respectively. Additionally, PET imaging with the integrin α6 targeted 18F-RWY enabled to visualize small HCC lesions with diameters approximately 0.2 cm that was hard to be distinguished from surround hepatic vascular by enhanced MRI with Gd-EOB-DTPA. These findings potentiate the use of integrin α6 targeted PET tracer 18F-RWY for the detection of HCC.",
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AU - Xiao, Yi Tai

AU - Li, Xin Ling

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AU - Zeng, Mu Sheng

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AB - Integrin α6 emerges to be a diagnostic biomarker for hepatocellular carcinoma (HCC). Here, we translated our previously identified integrin α6 targeted peptide RWY into a positron emission tomography (PET) tracer 18F-RWY for the detection of HCC lesions in following four HCC mouse models including subcutaneous, orthotopic, genetically engineered and chemical induced HCC mice. 18F-RWY produced high PET signals in liver tumor tissues that were reduced by blocking studies using nonradiolabeled RWY peptide. We compared the integrin α6 targeted PET tracer 18F-RWY with the integrin αvβ3-targeted PET tracer 18F-3PRGD2 and the clinical PET tracer 18F-FDG in chemical induced HCC mice. Among 12 HCC identified by enhanced magnetic resonance imaging (MRI) with hepatocellular specific gadoxetate disodium Gd-EOB-DTPA, the sensitivities of 18F-RWY, 18F-3PRGD2 and 18F-FDG were approximately 92%, 73% and 50% while the tumor-to-liver ratios were 4.36 ± 1.41, 1.97 ± 0.43 and 1.63 ± 0.23 respectively. Additionally, PET imaging with the integrin α6 targeted 18F-RWY enabled to visualize small HCC lesions with diameters approximately 0.2 cm that was hard to be distinguished from surround hepatic vascular by enhanced MRI with Gd-EOB-DTPA. These findings potentiate the use of integrin α6 targeted PET tracer 18F-RWY for the detection of HCC.

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