Simultaneous hyperpolarized 13C-pyruvate MRI and 18F-FDG-PET in cancer (hyperPET): feasibility of a new imaging concept using a clinical PET/MRI scanner

摘要

In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized ¹³C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and ¹⁸F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We have named this concept hyper PET. Intravenous injection of the hyperpolarized ¹³C-pyruvate results in an increase of ¹³C-lactate, ¹³C-alanine and ¹³C-CO2 (¹³C-HCO3) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization (DNP) and use of ¹³C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of ¹³C-pyruvate to ¹³C-lactate. In this study, we combined it with ¹⁸F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified local recurrence of a liposarcoma on the right forepaw was imaged using a combined PET/MR clinical scanner. PET was performed as a single-bed, 10 min acquisition, 107 min post injection of 310 MBq ¹⁸F-FDG. ¹³C-chemical shift imaging (CSI) was performed just after FDG-PET and 30 s post injection of 23 mL hyperpolarized ¹³C-pyruvate. Peak heights of ¹³C-pyruvate and ¹³C-lactate were quantified using a general linear model. Anatomic ¹H-MRI included axial and coronal T1 vibe, coronal T2-tse and axial T1-tse with fat saturation following gadolinium injection. In the tumor we found clearly increased ¹³C-lactate production, which also corresponded to high ¹⁸F-FDG uptake on PET. This is in agreement with the fact that glycolysis and production of lactate are increased in tumor cells compared to normal cells. Yet, most interestingly, also in the muscle of the forepaw of the dog high ¹⁸F-FDG uptake was observed. This was due to activity in these muscles prior to anesthesia, which was not accompanied by a similarly high ¹³C-lactate production. Accordingly, this clearly demonstrates how the Warburg Effect directly can be demonstrated by hyperpolarized ¹³C-pyruvate MRSI. This was not possible with ¹⁸F-FDG-PET imaging due to inability to discriminate between causes of increased glucose uptake. We propose that this new concept of simultaneous hyperpolarized ¹³C-pyruvate MRSI and PET may be highly valuable for image-based non-invasive phenotyping of tumors. This methods may be useful for treatment planning and therapy monitoring.