In Vivo Imaging of Hypoxia and Neoangiogenesis in Experimental Syngeneic Hepatocellular Carcinoma Tumor Model Using Positron Emission Tomography-Reference-Cited by-同舟云学术

In Vivo Imaging of Hypoxia and Neoangiogenesis in Experimental Syngeneic Hepatocellular Carcinoma Tumor Model Using Positron Emission Tomography

Published:2020-08-07 Issue: Volume:2020 Page:1-10
ISSN:2314-6133
Container-title:BioMed Research International
language:en
Short-container-title:BioMed Research International

Author:

Kis Adrienn¹²,Szabó Judit P.¹²,Dénes Noémi¹³,Vágner Adrienn⁴,Nagy Gábor⁴,Garai Ildikó¹⁴,Fekete Anikó¹,Szikra Dezső¹,Hajdu István¹⁵,Matolay Orsolya²⁶,Méhes Gábor²⁶,Mező Gábor⁷,Kertész István¹⁵,Trencsényi György¹²³^ORCID

Affiliation:

1. Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary

2. Doctoral School of Clinical Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary

3. Gyula Petrányi Doctoral School of Allergy and Clinical Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary

4. Scanomed Ltd, Nagyerdei St. 98, H-4032 Debrecen, Hungary

5. Doctoral School of Pharmaceutical Sciences, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary

6. Department of Pathology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary

7. MTA-ELTE, Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, Budapest, Hungary

Abstract

Introduction. Hypoxia-induced ανβ3 integrin and aminopeptidase N (APN/CD13) receptor expression play an important role in tumor neoangiogenesis. APN/CD13-specific 68Ga-NOTA-c(NGR), ανβ3 integrin-specific 68Ga-NODAGA-[c(RGD)]2, and hypoxia-specific 68Ga-DOTA-nitroimidazole enable the in vivo detection of the neoangiogenic process and the hypoxic regions in the tumor mass using positron emission tomography (PET) imaging. The aim of this study was to evaluate whether 68Ga-NOTA-c(NGR) and 68Ga-DOTA-nitroimidazole allow the in vivo noninvasive detection of the temporal changes of APN/CD13 expression and hypoxia in experimental He/De tumors using positron emission tomography. Materials and Methods. 5×106 hepatocellular carcinoma (He/De) cells were used for the induction of a subcutaneous tumor model in Fischer-344 rats. He/De tumor-bearing animals were anaesthetized, and 90 min after intravenous injection of 10.2±1.1 MBq 68Ga-NOTA-c(NGR) or 68Ga-NODAGA-[c(RGD)]2 (as angiogenesis tracers) or 68Ga-DOTA-nitroimidazole (for hypoxia imaging), whole-body PET/MRI scans were performed. Results. Hypoxic regions and angiogenic markers (αvβ3 integrin and APN/CD13) were determined using 68Ga-NOTA-c(NGR), 68Ga-DOTA-nitroimidazole, and 68Ga-NODAGA-[c(RGD)]2 in subcutaneously growing He/De tumors in rats. 68Ga-NOTA-c(NGR) showed the strong APN/CD13 positivity of He/De tumors in vivo, by which observation was confirmed by western blot analysis. By the qualitative analysis of PET images, heterogenous accumulation was found inside He/De tumors using all radiotracers. Significantly (p≤0.01) higher SUVmean and SUVmax values were found in the radiotracer avid regions of the tumors than those of the nonavid areas using hypoxia and angiogenesis-specific radiopharmaceuticals. Furthermore, a strong correlation was found between the presence of angiogenic markers, the appearance of hypoxic regions, and the tumor volume using noninvasive in vivo PET imaging. Conclusion. 68Ga-DOTA-nitroimidazole and 68Ga-NOTA-c(NGR) are suitable diagnostic radiotracers for the detection of the temporal changes of hypoxic areas and neoangiogenic molecule (CD13) expression, which vary during tumor growth in a hepatocellular carcinoma model.

Funder

Debreceni Egyetem

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

Link

http://downloads.hindawi.com/journals/bmri/2020/4952372.pdf

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