title: 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 [(99m)Tc]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.
authors.affiliation: Department of Nuclear Medicine, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK. sabina.dizdarevic@bsuh.nhs.uk
authors.forename: S
authors.initials: S
authors.lastname: Dizdarevic
authors.forename: A M
authors.initials: AM
authors.lastname: Peters
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D019450:Genes, MDR; D005838:Genotype; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D017256:Technetium Tc 99m Sestamibi
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D017256:Technetium Tc 99m Sestamibi