Monocarboxylate transporter 1 (MCT1) - a potential target for tumour imaging with PET
Tumour cell populations are heterogeneous. They contain glycolytic (hypoxic) and oxidative cells. Hypoxic tumour cells primarily use glucose for glycolytic energy production and release lactic acid, creating a lactate gradient that mirrors the oxygen gradient in the tumour. Although lactate is generally considered a waste product, it has been shown that it is a prominent substrate that fuels the oxidative metabolism of oxygenated tumour cells. Accordingly, there is a symbiosis in which glycolytic and oxidative tumour cells mutually regulate their access to energy substrates which is called Warburg effect. To accomplish this task, cancer cells upregulate proton-coupled membrane proteins called monocarboxylate transporters (MCTs). Consequently, elevated expressions of MCT1 and MCT4 have been identified in a large number of tumours. Certain tumours, such as gliomas and triple negative breast cancer, are especially difficult to treat due to unique metabolic features of these tumours. In particular, tumour hypoxia in these cancers can lead to treatment failure, relapse, and patient mortality as these cells are resistant to standard chemo- and radiation therapy. Consequently, the lactate transporters MCT1 and MCT4 are attractive targets for diagnosis and therapy of those tumours. Hence, inhibitors of MCT1 and/or MCT4 labeled with positron emitting radionuclides such as 11C and 18F have potential as imaging agents for brain tumours using PET.
Monocarboxylate transporters serve as lactate shuttles between various types of cancer cells and endothelial cells. MCT inhibition ledas to toxic lactate accumulation in cancer cells and to angiogenic effects.
(Modified from Draoui and Feron 2011)
Department of Biomedical Sciences, Medical School, University of Minnesota, USA (Prof. Lester Drewes and Dr. Shirisha Gurrapu)
- Alexander von Humboldt foundation