IMoST - MCT transporters targeting

Published on June 8, 2021 – Updated on July 20, 2021

The aim of this project is to develop radiofluorinated molecules that are specific substrates of MCT1 or MCT4, both lactate transporters. It will allow to visualise the tumour expression of these transporters by PET imaging. This functional imaging should therefore allow (i) a stratification of patients according to transporters expression with a prognostic value and (ii) the selection of patients who could benefit from a treatment based on specific inhibitors of both transporters.

MCTs convey lactate exchanges in tumors. The model represents notably lactate exchanges between oxidative and glycolytic tumor cells and in the metabolic exploitation of stromal cells by oxidative tumor cells.

MCTs convey lactate exchanges in tumors. The model represents notably lactate exchanges between oxidative and glycolytic tumor cells and in the metabolic exploitation of stromal cells by oxidative tumor cells.

Breast cancer is a major health issue; especially for certain aggressive and difficult to treat subtypes such as triple negative breast cancer (TNBC). A large part of breast cancer research is currently focused on this aggressive form. In order to discover new therapies and to improve the prognosis and survival of patients, new targets are being studied in preclinical and clinical trials. One of these new targets of interest is the monocarboxylate membrane solute transporter MCT4, which allows the expulsion of lactate produced by cancer cells in hypoxic zones. This transporter is a member of the SLC16A family, which includes MCT1, which also plays a major role in many cancers, including breast one (PMID: 25449995).

MCT4 has been clearly shown to be a factor of poor prognostic in TNBC. Several inhibitors have been developed and in clinical trials, including the MCT1/MCT2 inhibitor AZD3965, which is currently in phase I/II clinical trials. This treatment seems promising, and it is interesting to develop a diagnostic tool to define the patients eligible for this treatment but also to monitor its effectiveness. The development of a radiotracer allowing the functional imaging of these membrane transporters thus appears to be an indispensable tool today.

We are therefore developing a molecular platform based on a specific competitive inhibitor structural motif of MCT4 to develop new iodinated or fluorinated radiotracers. Sufficient accumulation of these labelled molecules with adapted distribution kinetics will allow the imaging of positive tumours.