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Molecular Imaging and Biology

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26.08.2019 | Research Article

Noninvasive Classification of Human Triple Negative Breast Cancer by PET Imaging with GRP78-Targeted Molecular Probe [⁶⁸Ga]DOTA-VAP

verfasst von: Haitao Zhao, Huannan Meng, Jun Wen, Cheng Wang, Jianjun Liu, Gang Huang

Erschienen in: Molecular Imaging and Biology | Ausgabe 3/2020

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Abstract

Purpose

There is currently no effective noninvasive method for accurate molecular typing of triple negative breast cancer (TNBC) except needle biopsy. Glucoregulated Protein 78 (GRP78) is overexpressed in TNBC cells and tumors which closely related to the invasion, metastasis, and drug resistance of cancer. Meanwhile, it has been verified that VAP peptide bind specifically to GRP78 in vitro and in vivo. In this study, we constructed a GRP78-targeted molecular probe Ga-68-radiolabeled DOTA-VAP conjugate ([⁶⁸Ga]DOTA-VAP) based on VAP peptide, and evaluated its potential to distinguish TNBC from non-TNBC tumors.

Procedures

DOTA-VAP was synthesized and then radiolabeled with Ga-68 to obtain [⁶⁸Ga]DOTA-VAP. The expression of GRP78 in TNBC MDA-MB-231 and non-TNBC MCF-7 cells was validated by Western Blot, and cell binding or uptake experiments with both [⁶⁸Ga]DOTA-VAP and 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) were also performed. Biodistribution analysis and positron emission tomography (PET) imaging of [⁶⁸Ga]DOTA-VAP were carried out in subcutaneous MDA-MB-231 and MCF-7 human breast cancer tumor models with [¹⁸F]FDG PET imaging as comparison.

Results

[⁶⁸Ga]DOTA-VAP was prepared with high radiochemical purity which showed excellent stability in vitro. The MDA-MB-231 tumors were clearly visualized by [⁶⁸Ga]DOTA-VAP PET imaging with a low background, except for the relatively high liver uptake. Cells and tumors of MDA-MB-231 could be distinguished from MCF-7 by [⁶⁸Ga]DOTA-VAP instead of [¹⁸F]FDG. Biodistribution results were consistent with the imaging results. The blocking study with excess cold peptide showed significantly reduced tumor uptake, which indicated the specificity of [⁶⁸Ga]DOTA-VAP targeting MDA-MB-231 tumors in vivo.

Conclusions

GRP78-targeted PET imaging with [⁶⁸Ga]DOTA-VAP provided an effective approach for the noninvasive accurate classification of TNBC from other breast cancer subtypes comparing with [¹⁸F]FDG. GRP78 may be a potential target for the diagnosis and treatment of TNBC. For clinical transformation, efforts should be made to overcome deficiencies of [⁶⁸Ga]DOTA-VAP such as relative high uptake in normal tissues.

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Titel: Noninvasive Classification of Human Triple Negative Breast Cancer by PET Imaging with GRP78-Targeted Molecular Probe [68Ga]DOTA-VAP
verfasst von: Haitao Zhao
Huannan Meng
Jun Wen
Cheng Wang
Jianjun Liu
Gang Huang
Publikationsdatum: 26.08.2019
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 3/2020
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-019-01416-4

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Noninvasive Classification of Human Triple Negative Breast Cancer by PET Imaging with GRP78-Targeted Molecular Probe [⁶⁸Ga]DOTA-VAP

Abstract

Purpose

Procedures

Results

Conclusions

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Abstract

Purpose

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