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

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 6; p. 1568
• Main Authors: Lu, Yun, Li, Meng, Massicano, Adriana V F, Song, Patrick N, Mansur, Ameer, Heinzman, Katherine A, Larimer, Benjamin M, Lapi, Suzanne E, Sorace, Anna G
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 12-03-2021; MDPI AG
• Subjects: Animals; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Phytogenic - therapeutic use; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cell Line, Tumor; FDG-PET; Female; Fluorodeoxyglucose F18; HER2+ breast cancer; heterogeneity; Humans; Mice; Mice, Nude; Molecular Imaging; Paclitaxel - therapeutic use; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radioisotopes; Radiopharmaceuticals; Receptor, ErbB-2 - metabolism; Treatment Outcome; Xenograft Model Antitumor Assays; Zirconium; FDG-PET; HER2+ breast cancer; molecular imaging; positron emission tomography; heterogeneity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26061568

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 [
Zr]-pertuzumab PET/CT imaging. PTX treatment response was quantified by [
F]-fluorodeoxyglucose ([
F]-FDG) PET/CT imaging. Spearman's correlation, Kendall's tau, Kolmogorov-Smirnov test, and ANOVA were used for statistical analysis. [
Zr]-pertuzumab mean standard uptake values (SUV
) 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. [
F]-FDG SUV
changes were negatively correlated with [
Zr]-pertuzumab SUV
(r = -0.5887,
= 0.0030). The baseline [
F]-FDG SUV
was negatively correlated with initial [
Zr]-pertuzumab SUV
(r = -0.6852,
= 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.