Abstract

Molecular imaging technique is an attractive tool to detect liver disease at early stage. This study aims to develop a simultaneous dual-isotope single photon emission computed tomography (SPECT)/CT imaging method to assist diagnosis of hepatic tumor and liver fibrosis. Animal models of liver fibrosis and orthotopic human hepatocellular carcinoma (HCC) were established. The tracers of 131I-NGA and 99mTc-3P-RGD2 were selected to target asialoglycoprotein receptor (ASGPR) on the hepatocytes and integrin αvβ3 receptor in tumor or fibrotic liver, respectively. SPECT imaging and biodistribution study were carried out to verify the feasibility and superiority. As expected, 99mTc-3P-RGD2 had the ability to evaluate liver fibrosis and detect tumor lesions. 131I-NGA showed that it was effective in assessing the anatomy and function of the liver. In synchronized dual-isotope SPECT/CT imaging, clear fusion images can be got within 30 minutes for diagnosing liver fibrosis and liver cancer. This new developed imaging approach enables the acquisition of different physiological information for diagnosing liver fibrosis, liver cancer and evaluating residual functional liver volume simultaneously. So synchronized dual-isotope SPECT/CT imaging with 99mTc-3P-RGD2 and 131I-NGA is an effective approach to detect liver disease, especially liver fibrosis and liver cancer.

Highlights

  • Molecular imaging technique is an attractive tool to detect liver disease at early stage

  • Recent studies showed that radiolabeled RGD useful for early detection of integrin αvβ3-positive tumors and for staging liver fibrosis by SPECT8,20–22

  • 99mTc-3P-RGD2 and 131I-neogalactosyl albumin (NGA) were more than 95% which determined by high performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) (Fig. 1b,c and Fig. S1)

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Summary

Introduction

Molecular imaging technique is an attractive tool to detect liver disease at early stage. This study aims to develop a simultaneous dual-isotope single photon emission computed tomography (SPECT)/CT imaging method to assist diagnosis of hepatic tumor and liver fibrosis. 99mTc-3P-RGD2 had the ability to evaluate liver fibrosis and detect tumor lesions. Synchronized dual-isotope SPECT/CT imaging with 99mTc-3P-RGD2 and 131I-NGA is an effective approach to detect liver disease, especially liver fibrosis and liver cancer. Recent studies showed that radiolabeled RGD useful for early detection of integrin αvβ3-positive tumors and for staging liver fibrosis by SPECT8,20–22. SPECT imaging with dual-probe 131I-NGA and 99mTc3P-RGD2 (Fig. 1a) were investigated to help the early diagnosis of hepatic diseases, accurate evaluation of functional status and better define of both tumor size and boundary between functional liver and lesions

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