Background/Aim
[18F]Fluoro-2-deoxyglucose positron emission tomography computed tomography (FDG-PET/CT) is routinely used in the diagnosis and monitoring of patients with melanoma. However, it remains unclear how FDG-PET/CT parameters relate to the utilisation of glucose in vivo. In the MetaMel Study (NCT05570227), 13C-glucose is infused in patients undergoing surgical resection, enabling the assessment of glucose utilisation in vivo in melanoma. This project aims to explore whether FDG-PET/CT parameters correlate with metabolic features of melanoma.
Methods
Patients received intravenous 13C-glucose, first as an 8g bolus followed by infusion of 4g/hour for 2-3 hours prior to surgical resection. Blood and tumour samples were obtained to analyse enrichment of 13C-labelled metabolites via gas-chromatography mass spectrometry (GC-MS). Baseline FDG-PET/CT and clinical parameters were obtained for each patient. Tumour samples were also processed to develop parallel patient-derived xenografts (PDXs), which subsequently underwent 13C-glucose infusion and FDG-PET/CT imaging. The FDG-PET/CT parameters extracted were: maximum and mean standardised uptake values (SUVmax/mean); metabolic tumour volume (MTV); total lesion glycolysis (TLG). These parameters were correlated with tumour metabolic parameters, including the following ratios: tumour/serum glucose [M+6]; citrate [M+2]/pyruvate [M+3]; lactate [M+3]/pyruvate [M+3]. FDG-PET parameters between patients and PDXs were also correlated.
Results
Fourteen patients have received a [13C]-glucose infusion (with sampling from 2 primary lesions, 10 lymph nodes, 3 in-transits, 3 distant metastasis). MS data is currently available for 8 patients, with analyses ongoing. We have also successfully established and imaged 20 PDXs (derived from 5 patient samples). Preliminary analyses show no correlation between FDG-PET/CT and mass spectrometry parameters, including between SUVmax and tumour/serum glucose [M+6], which may be surrogates of tumour glucose uptake. We observed a similar trend of SUVmax in patients and their matched PDXs, comparison with mass spectrometry parameters in these models is underway.
Conclusion
In this initial exploratory analysis, it appears that FDG-PET/CT parameters do not correlate with metabolic features of melanoma assessed by mass spectrometry, illustrating the potential for 13C-glucose tracing to provide additional insights into melanoma metabolism in vivo.