Early therapy evaluation of intra-arterial trastuzumab injection in a human breast cancer xenograft model using multiparametric MR imaging

Bo Kyu Kim; Byungjun Kim; Sung-Hye You; Moon-Sun Jang; Geun Ho Im; Keon-Ha Kim

doi:10.1371/journal.pone.0300171

Early therapy evaluation of intra-arterial trastuzumab injection in a human breast cancer xenograft model using multiparametric MR imaging

PLoS One. 2024 May 3;19(5):e0300171. doi: 10.1371/journal.pone.0300171. eCollection 2024.

Authors

Bo Kyu Kim¹, Byungjun Kim¹, Sung-Hye You¹, Moon-Sun Jang², Geun Ho Im³, Keon-Ha Kim⁴

Affiliations

¹ Department of Radiology, Korea University Anam Hospital, Seoul, Korea.
² Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine and Center for Molecular and Cellular Imaging, Samsung Biomedical Research Institute, Seoul, Korea.
³ Center for Neuroscience Imaging Research, SungKyunkwan University, Suwon, Korea.
⁴ Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

Purpose: To investigate the treatment efficacy of intra-arterial (IA) trastuzumab treatment using multiparametric magnetic resonance imaging (MRI) in a human breast cancer xenograft model.

Materials and methods: Human breast cancer cells (BT474) were stereotaxically injected into the brains of nude mice to obtain a xenograft model. The mice were divided into four groups and subjected to different treatments (IA treatment [IA-T], intravenous treatment [IV-T], IA saline injection [IA-S], and the sham control group). MRI was performed before and at 7 and 14 d after treatment to assess the efficacy of the treatment. The tumor volume, apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) MRI parameters (Ktrans, Kep, Ve, and Vp) were measured.

Results: Tumor volumes in the IA-T group at 14 d after treatment were significantly lower than those in the IV-T group (13.1 mm3 [interquartile range 8.48-16.05] vs. 25.69 mm3 [IQR 20.39-30.29], p = 0.005), control group (IA-S, 33.83 mm3 [IQR 32.00-36.30], p<0.01), and sham control (39.71 mm3 [IQR 26.60-48.26], p <0.001). The ADC value in the IA-T group was higher than that in the control groups (IA-T, 7.62 [IQR 7.23-8.20] vs. IA-S, 6.77 [IQR 6.48-6.87], p = 0.044 and vs. sham control, 6.89 [IQR 4.93-7.48], p = 0.004). Ktrans was significantly decreased following the treatment compared to that in the control groups (p = 0.002 and p<0.001 for vs. IA-S and sham control, respectively). Tumor growth was decreased in the IV-T group compared to that in the sham control group (25.69 mm3 [IQR 20.39-30.29] vs. 39.71 mm3 [IQR 26.60-48.26], p = 0.27); there was no significant change in the MRI parameters.

Conclusion: IA treatment with trastuzumab potentially affects the early response to treatment, including decreased tumor growth and decrease of Ktrans, in a preclinical brain tumor model.

Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents, Immunological / administration & dosage
Antineoplastic Agents, Immunological / therapeutic use
Breast Neoplasms* / diagnostic imaging
Breast Neoplasms* / drug therapy
Breast Neoplasms* / pathology
Cell Line, Tumor
Female
Humans
Injections, Intra-Arterial*
Mice
Mice, Inbred BALB C
Mice, Nude*
Multiparametric Magnetic Resonance Imaging / methods
Trastuzumab* / administration & dosage
Trastuzumab* / pharmacology
Trastuzumab* / therapeutic use
Tumor Burden / drug effects
Xenograft Model Antitumor Assays*

Substances

Trastuzumab
Antineoplastic Agents, Immunological

Grants and funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT). (2017R1C1B5017922). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.