Abstract

Background: Gd-DOTA is a micromolecular compound that is not specific for HER2+ breast cancer cells. It is not retained in the tissues and easily excreted via kidney and stool leading to suboptimal imaging. Conjugation of Gd-DOTA with trastuzumab by dendrimer will create a macromolecule and specifically bind to HER2 receptor. This study aimed to evaluate enhancing intensity of Gd-Dota-Dendrimer-Trastuzumab by Magnetic Resonance Imaging (MRI) in HER2+ breast cancer cells HCC1954 in apple scaffold.

Methods: HER2+ breast cancer cell, HCC-1954 was culture in 3 dimensional culture system using apple scaffold. Intensity of contrast agents were evaluated using MRI. Cytotoxic activity of Gd-Dota-Dendrimer-Trastuzumab was evaluated in HER2+ breast cancer cells (HCC-1954 and SKBR-3) and HER2- breast cancer cell (MCF-7) using MTT assay. This study was an experimental test using Generalized Estimating Equation (GEE) method with statistical test of Generalized Linear Model (GLM) with exchangeable matrix correlation structure.

Result: We confirmed that HCC-1954 cells were grown in apple scaffold and increased intensity of MRI image. Interestingly, Gd-Dota-Dendrimer-Trastuzumab tended to increase intensity of MRI image compared to Gd-Dota using HCC-1954 cells in apple scaffold, although the difference was not significant (p>0.05). Importantly, the HER2+ sensitive to trastuzumab cells, SKBR3 cells were still sensitive to Gd-Dota-Dendrimer-Trastuzumab but not the HCC-1954 and MCF-7 cells.

Conclusion: Gd-Dota-Dendrimer-Trastuzumab was potentially increase MRI intensity in HER2+ breast cancer cells.

Keywords: Apple scaffold; HER2+ breast cancer; Gd-DOTADendrimer-Trastuzumab; Magnetic Resonance Imaging (MRI)