Diagnosis of cancer multidrug resistance by bacterium-mediated imaging

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• 作者：Omar Anwar Elkadi^a ; ^b ; ^{Omar.elkadi@live.com" class="auth_mail" title="E-mail the corresponding author} ; Muhammad Abdelbasset^a
• 关键词：MDR ; multidrug resistance ; ABC ; Adenosine triphosphate Binding Cassette ; Pgp ; P-glycoprotein ; MRP ; multidrug resistance associated protein ; MIC ; minimum inhibitory concentration ; [99mTc] MIBI ; technetium labeled sestamibi ; MRI ; magnetic resonance imaging ; PET ; positron emission tomography ; BLI ; bioluminescent imaging ; FLI ; fluorescent imaging
• 刊名：Medical Hypotheses
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：89
• 期：Complete
• 页码：11-15
• 全文大小：420 K

文摘

Multidrug resistance (MDR) is a phenomenon expressed by many tumors affecting the chemotherapy efficacy, treatment decision, and the disease prognosis. Considering its great implication, non-invasive approaches are needed to identify this phenomenon in early stages of the disease. This article discusses the potential of the emerging non-invasive bacterium-mediated imaging of cancer in diagnosis of MDR. This potential is derived from the effect of cancer MDR on the pharmacokinetics of certain antibiotics, which are substrates of the MDR proteins. Since MDR proteins actively pump their substrates outside the resistant cancer cells, the elimination of the employed reporter bacteria, proliferating within MDR cancer cells, would require a larger dose of these antibiotics compared to those inside non-MDR cancer cells. These bacteria bear reporter genes that produce specific signals such as bioluminescent, fluorescent, magnetic, or radioactive signals that can be detected by non-invasive imaging modalities. Therefore, the presence, degree, and mechanism of MDR can be estimated by comparing the concentration of the employed antibiotic, required to cease these signals (reflecting the elimination of the bacteria), to a pre-determined reference. The real time imaging of MDR cancer and the early diagnosis of MDR, offered by this approach, would provide a better tool for preclinical studies of MDR, and allow a prompt choice of the most appropriate therapy.