Abstract
99mTc-sestamibi (99mTc-MIBI) is a substrate for the P-glycoprotein (P-gp) pump but it is not known whether it is a substrate for the multidrug resistance-associated protein (MRP) pump. Therefore, 99mTc-MIBI was evaluated in the GLC4 cell line and its doxorubicin-resistant MRP-, but not P-gp-, overexpressing GLC4/ADR sublines as well as in the S1 cell line and its MRP-transfected subline S1-MRP. 99mTc-MIBI concentration decreased in the GLC4/ADR sublines with increasing MRP overexpression and was lower in S1-MRP than in S1. 99mTc-MIBI plus vincristine increased 99mTc-MIBI concentration in GLC4 lines compared with 99mTc-MIBI alone. 99mTc-MIBI efflux raised with increasing MRP expression in the GLC4 lines. Glutathione depletion elevated 99mTc-MIBI concentration in GLC4/ADR150x. Cross resistance for 99Tc-MIBI, used to test cytotoxicity of the Tc compound, was observed in GLC4/ADR150x vs GLC4. 99Tc-MIBI induced a synergistic effect on vincristine cytotoxicity in GLC4/ADR150x. These results show that 99mTc-MIBI is involved in MRP-mediated efflux. The fact that 99mTc-MIBI efflux is influenced by MDR1 and MRP expression must be taken into account when this gamma-rays-emitting complex is tested for tumour efflux measurements.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hendrikse, N., Franssen, E., van der Graaf, W. et al. 99mTc-sestamibi is a substrate for P-glycoprotein and the multidrug resistance-associated protein. Br J Cancer 77, 353–358 (1998). https://doi.org/10.1038/bjc.1998.57
Issue Date:
DOI: https://doi.org/10.1038/bjc.1998.57
This article is cited by
-
Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives
Journal of Cancer Research and Clinical Oncology (2022)
-
In vivo characterization of [18F]AVT-011 as a radiotracer for PET imaging of multidrug resistance
European Journal of Nuclear Medicine and Molecular Imaging (2020)
-
PET Radiopharmaceuticals for Imaging Chemotherapy-Induced Cardiotoxicity
Current Cardiology Reports (2020)
-
Correlation of 99mTc-sestamibi uptake in renal masses with mitochondrial content and multi-drug resistance pump expression
EJNMMI Research (2017)
-
Imaging P-glycoprotein function in rats using [11C]-N-desmethyl-loperamide
Annals of Nuclear Medicine (2013)