Probing lactate secretion in tumours with hyperpolarised NMR

Area of Science:

• Biomedical Imaging
• Cancer Metabolism
• Molecular Imaging

Background:

• Tumors rely heavily on glycolysis, producing lactate.
• Monocarboxylate transporters (MCTs) are crucial for exporting lactate from cancer cells.
• Understanding MCT function is vital for cancer therapy.

Purpose of the Study:

• To develop and validate a novel MRI technique for measuring MCT-mediated metabolite transport in vivo.
• To quantify the efflux rates of lactate and alanine in a rat mammary carcinoma model.
• To assess the potential of this technique for monitoring MCT-targeted cancer therapies.

Main Methods:

• Utilized hyperpolarized [1-(13)C]pyruvate and a Gd(III) complex for in vivo MRI in rats with mammary carcinoma.
• Employed a specialized pulse sequence to isolate lactate transport.
• Acquired slice-selective spectra and spatially resolved maps of transporter activity.

Main Results:

• Demonstrated a significant increase in decay rate for lactate, indicating rapid cellular efflux.
• Observed an unaltered signal for alanine, suggesting slower efflux.
• Successfully mapped apparent membrane transporter activity in vivo.

Conclusions:

• The developed hyperpolarized MRI technique can effectively measure MCT activity and metabolite transport rates.
• This method offers insights into tumor metabolism and holds promise for evaluating treatment response in MCT-targeted therapies.
• Provides valuable data on signal kinetics in hyperpolarized [1-(13)C]pyruvate studies.