Imaging of multidrug resistance in cancer

Abstract

Primary intrinsic and/or acquired multidrug resistance (MDR) is the main obstacle to successful cancer treatment. Functional molecular imaging of MDR in cancer using single photon or positron emitters may be helpful to identify multidrug-resistant tumours and predict not only those patients who are resistant to treatment, with a clinically unfavourable prognosis, but also those who are susceptible to the development of drug toxicity or even certain tumours . Variations in the mdr1 gene product may directly affect the therapeutic effectiveness, and single nucleotide polymorphisms for the mdr1 gene may be associated with altered oral bioavailability of MDR1 substrates, drug resistance, and a susceptibility to some human diseases. The challenge of translating the concept of MDR modulation in vivo involves a complex cellular interplay between both malignant and normal cells. Integration and correlation of functional single photon emission tomography or positron emission tomography imaging findings with mdr1 genotype and clinical data may contribute to efficient management by selecting cancer patients with the appropriate molecular phenotype for maximal individual therapeutic benefit, as well as those who are non-responders. This review describes a role for functional imaging of classical mechanisms of MDR with an emphasis on readily available [99mTc]MIBI scintigraphy. MIBI scintigraphy has been shown to be a non-invasive cost-effective in vivo assay of ATP-binding cassette transporters associated with MDR in cancer, including P-glycoprotein, multidrug-resistant protein 1 and breast cancer resistant protein. New imaging agents for molecular targets such as vascular endothelial growth factor and HER2 receptors, may potentially be combined with MDR imaging substrates to more accurately predict the therapeutic response to anticancer drugs, guiding individualised treatment while minimising the economic health costs of ineffective therapy in an era of personalised medicine.

Establishment of Paclitaxel-resistant Breast Cancer Cell Line and Nude Mice Models, and Underlying Multidrug Resistance Mechanisms in Vitro and in Vivo

“…Although the prognosis and treatment of breast cancer continue to evolve, MDR in cancer is still frequently occurred and becomes the crucial obstacle to limit the effectiveness of clinical antitumor drug treatment (Saeki et al, 2005;Dizdarevic and Peters, 2011). It has been well known that the mechanisms and signal pathways of MDR is complicated and multifactorial, it potentially involved alterations in the expression of various proteins.…”

Preoperative Localization of Abnormal Parathyroid Glands

“…However, 99m Tc-sestamibi is released much faster from thyroid than from parathyroid tissue, a pathophysiologic pattern possibly related to down-regulation in the parathyroid of the membrane-associated P-glycoprotein system related to multidrug resistance, a system for which 99m Tc-sestamibi is also a substrate. [58][59][60][61] This differential washout rate of 99m Tc-sestamibi from the thyroid relative to the parathyroid permits parathyroid scintigraphy to be performed with this single tracer, according to the so-called dual-phase 99m Tc-sestamibi acquisition protocol. As originally described by Taillefer et al, 54 planar imaging of the neck and thorax is acquired at 15 minutes, then 2-3 hours after the i.v.…”

Drug Efflux Transporters and Multidrug Resistance in Acute Leukemia: Therapeutic Impact and Novel Approaches to Mediation

“…Finally, the combination of single-photon emission computed tomography, positron emission tomography, and other imaging techniques with genetic data, guided by the findings of preclinical and clinical studies of MDR, may prove important for the selection of optimal treatments for patients who demonstrate particular MDR phenotypes (Dizdarevic and Peters, 2011).…”

“…Positron emission tomography using [ 18 F]fluoroethyl compounds (Kawamura et al, 2011) and 99m Tc-hexakis-2-methoxyisobutylisonitrile scintigraphy (Dizdarevic and Peters, 2011) were used recently to assess the in vivo function of P-gp and BCRP, whereas another study suggested that MDR could be assessed by using a carbon nanotube-drug supramolecular nanocomposite electrochemical sensor, as demonstrated with sensitive and MDR K562 leukemia cells (Zhang et al, 2011a). Finally, the combination of single-photon emission computed tomography, positron emission tomography, and other imaging techniques with genetic data, guided by the findings of preclinical and clinical studies of MDR, may prove important for the selection of optimal treatments for patients who demonstrate particular MDR phenotypes (Dizdarevic and Peters, 2011).…”