[<sup>89</sup>Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models

Paclitaxel (PTX) treatment efficacy varies in breast cancer, yet the underlying mechanism for variable response remains unclear. This study evaluates whether human epidermal growth factor receptor 2 (HER2) expression level utilizing advanced molecular positron emission tomography (PET) imaging is co...

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Main Authors: Yun Lu, Meng Li, Adriana V. F. Massicano, Patrick N. Song, Ameer Mansur, Katherine A. Heinzman, Benjamin M. Larimer, Suzanne E. Lapi, Anna G. Sorace
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/6/1568
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author Yun Lu
Meng Li
Adriana V. F. Massicano
Patrick N. Song
Ameer Mansur
Katherine A. Heinzman
Benjamin M. Larimer
Suzanne E. Lapi
Anna G. Sorace
author_facet Yun Lu
Meng Li
Adriana V. F. Massicano
Patrick N. Song
Ameer Mansur
Katherine A. Heinzman
Benjamin M. Larimer
Suzanne E. Lapi
Anna G. Sorace
author_sort Yun Lu
collection DOAJ
description Paclitaxel (PTX) treatment efficacy varies in breast cancer, yet the underlying mechanism for variable response remains unclear. This study evaluates whether human epidermal growth factor receptor 2 (HER2) expression level utilizing advanced molecular positron emission tomography (PET) imaging is correlated with PTX treatment efficacy in preclinical mouse models of HER2+ breast cancer. HER2 positive (BT474, MDA-MB-361), or HER2 negative (MDA-MB-231) breast cancer cells were subcutaneously injected into athymic nude mice and PTX (15 mg/kg) was administrated. In vivo HER2 expression was quantified through [<sup>89</sup>Zr]-pertuzumab PET/CT imaging. PTX treatment response was quantified by [<sup>18</sup>F]-fluorodeoxyglucose ([<sup>18</sup>F]-FDG) PET/CT imaging. Spearman’s correlation, Kendall’s tau, Kolmogorov–Smirnov test, and ANOVA were used for statistical analysis. [<sup>89</sup>Zr]-pertuzumab mean standard uptake values (SUV<sub>mean</sub>) of BT474 tumors were 4.9 ± 1.5, MDA-MB-361 tumors were 1.4 ± 0.2, and MDA-MB-231 (HER2−) tumors were 1.1 ± 0.4. [<sup>18</sup>F]-FDG SUV<sub>mean</sub> changes were negatively correlated with [<sup>89</sup>Zr]-pertuzumab SUV<sub>mean</sub> (r = −0.5887, <i>p</i> = 0.0030). The baseline [<sup>18</sup>F]-FDG SUV<sub>mean</sub> was negatively correlated with initial [<sup>89</sup>Zr]-pertuzumab SUV<sub>mean</sub> (r = −0.6852, <i>p</i> = 0.0002). This study shows PTX treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models. Molecular imaging provides a non-invasive approach to quantify biological interactions, which will help in identifying chemotherapy responders and potentially enhance clinical decision-making.
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spelling doaj.art-8486229e4f754d789d946344429c7cbc2023-11-21T10:17:59ZengMDPI AGMolecules1420-30492021-03-01266156810.3390/molecules26061568[<sup>89</sup>Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse ModelsYun Lu0Meng Li1Adriana V. F. Massicano2Patrick N. Song3Ameer Mansur4Katherine A. Heinzman5Benjamin M. Larimer6Suzanne E. Lapi7Anna G. Sorace8Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Radiology, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Radiology, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Radiology, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Radiology, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Radiology, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Radiology, University of Alabama at Birmingham, Birmingham, AL 35233, USAPaclitaxel (PTX) treatment efficacy varies in breast cancer, yet the underlying mechanism for variable response remains unclear. This study evaluates whether human epidermal growth factor receptor 2 (HER2) expression level utilizing advanced molecular positron emission tomography (PET) imaging is correlated with PTX treatment efficacy in preclinical mouse models of HER2+ breast cancer. HER2 positive (BT474, MDA-MB-361), or HER2 negative (MDA-MB-231) breast cancer cells were subcutaneously injected into athymic nude mice and PTX (15 mg/kg) was administrated. In vivo HER2 expression was quantified through [<sup>89</sup>Zr]-pertuzumab PET/CT imaging. PTX treatment response was quantified by [<sup>18</sup>F]-fluorodeoxyglucose ([<sup>18</sup>F]-FDG) PET/CT imaging. Spearman’s correlation, Kendall’s tau, Kolmogorov–Smirnov test, and ANOVA were used for statistical analysis. [<sup>89</sup>Zr]-pertuzumab mean standard uptake values (SUV<sub>mean</sub>) of BT474 tumors were 4.9 ± 1.5, MDA-MB-361 tumors were 1.4 ± 0.2, and MDA-MB-231 (HER2−) tumors were 1.1 ± 0.4. [<sup>18</sup>F]-FDG SUV<sub>mean</sub> changes were negatively correlated with [<sup>89</sup>Zr]-pertuzumab SUV<sub>mean</sub> (r = −0.5887, <i>p</i> = 0.0030). The baseline [<sup>18</sup>F]-FDG SUV<sub>mean</sub> was negatively correlated with initial [<sup>89</sup>Zr]-pertuzumab SUV<sub>mean</sub> (r = −0.6852, <i>p</i> = 0.0002). This study shows PTX treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models. Molecular imaging provides a non-invasive approach to quantify biological interactions, which will help in identifying chemotherapy responders and potentially enhance clinical decision-making.https://www.mdpi.com/1420-3049/26/6/1568positron emission tomographyFDG-PETheterogeneityHER2+ breast cancermolecular imaging
spellingShingle Yun Lu
Meng Li
Adriana V. F. Massicano
Patrick N. Song
Ameer Mansur
Katherine A. Heinzman
Benjamin M. Larimer
Suzanne E. Lapi
Anna G. Sorace
[<sup>89</sup>Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models
Molecules
positron emission tomography
FDG-PET
heterogeneity
HER2+ breast cancer
molecular imaging
title [<sup>89</sup>Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models
title_full [<sup>89</sup>Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models
title_fullStr [<sup>89</sup>Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models
title_full_unstemmed [<sup>89</sup>Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models
title_short [<sup>89</sup>Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models
title_sort sup 89 sup zr pertuzumab pet imaging reveals paclitaxel treatment efficacy is positively correlated with her2 expression in human breast cancer xenograft mouse models
topic positron emission tomography
FDG-PET
heterogeneity
HER2+ breast cancer
molecular imaging
url https://www.mdpi.com/1420-3049/26/6/1568
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