Page 32 - ARNM-2-1

Advances in Radiotherapy &

Nuclear Medicine

ORIGINAL RESEARCH ARTICLE
Evaluation of multidrug resistance in tumors

using 99m Tc-doxorubicin

Bianca Gutfilen *, Sergio Augusto Lopes de Souza , Thiago Barboza ,
1
1
1
2
Bruna Fortunato Novis , Claudia Lopes Rodrigues Chagas ,
1
Maria Verônica Fonseca Torres de Oliveira , and Vivian M. Rumjanek 2
1
1 Laboratory of Labeling Cells and Molecules, Department of Radiology, Federal University of Rio de
Janeiro, Rio de Janeiro, Brazil
2 Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Abstract

Doxorubicin (DOX) is a potent chemotherapeutic agent used as the first-choice drug
in treating different types of cancer, such as leukemia, lymphoma, and breast cancer,
among others. However, the development of multidrug resistance represents a
significant obstacle to the successful treatment of tumors. In this study, we assessed
whether labeled DOX could be uptaken by susceptible and multidrug-resistant cell
lines and by tumors in vivo in animals. The efficiency of DOX labeling was maintained
at around 90% in this work. To evaluate the effect of 99m Tc-DOX on cells expressing
active P-glycoprotein (Pgp), we utilized cultured human chronic myeloid leukemia
K562 cells and the resistant counterpart Lucena 1 cells. Lucena 1 cell line showed
overexpression of Pgp that was not observed in K562. Our results suggested that
the resistance to labeled or unlabeled DOX can be reversed by Pgp inhibition and
can be easily detected. In conclusion, administering 99m Tc-DOX into mice enables the
*Corresponding author: differentiation between multidrug-resistant tumors in a non-invasive way and the
Bianca Gutfilen
(bgutfilen@hucff.ufrj.br) evaluation of tumor resistance and possible chemosensitizers.
Citation: Gutfilen B, de Souza
SAL, Barboza T, et al. Evaluation of Keywords: Doxorubicin; Multidrug resistance; Tc-99m; Tc-Doxorubicin
99m
multidrug resistance in tumors using
99m Tc-doxorubicin. Adv Radiother
Nucl Med. 2024;2(1):2822
https://doi.org/10.36922/arnm.2822
Received: January 25, 2024 1. Introduction
Accepted: March 28, 2024 A biomarker is an indicator of physiologic or pathogenic processes or biological
responses to a therapeutic intervention that can be objectively measured and evaluated.
Published Online: April 3, 2024
Measuring biomarkers can help with disease detection, treatment risk evaluation, or
Copyright: © 2024 Author(s). treatment effectiveness determination. In the case of cancer, anthracyclines such as
This is an Open-Access article
distributed under the terms of the doxorubicin (DOX) are part of the front-line therapy used to treat several malignancies,
Creative Commons Attribution including leukemia, lymphomas, soft-tissue sarcomas, breast carcinoma, and other
License, permitting distribution, solid tumors. DOX was added to the armada of cancer therapy in the late 1960s, and
and reproduction in any medium,
provided the original work is the comprehensive investigations of its pharmacokinetics have enabled a more in-depth
properly cited. understanding of this medication. DOX can be administered as a single agent or in
Publisher’s Note: AccScience combination with other chemotherapeutic agents. Although DOX is also used for
Publishing remains neutral with treating other tumors such as ovarian carcinoma, liver cancer, and stomach cancer, it is
regard to jurisdictional claims in
published maps and institutional not the primary choice in the clinical treatment for these cancers due to the emergence
affiliations. of drug resistance. 1-3

Volume 2 Issue 1 (2024) 1 https://doi.org/10.36922/arnm.2822