[${}^{68}$Ga]Ga-NODAGA-E[(cRGDyK)]${}_2$ PET and hyperpolarized [1-${}^{13}$C] pyruvate MRSI (hyperPET) in canine cancer patients: simultaneous imaging of angiogenesis and the Warburg effect

Cancer has a multitude of phenotypic expressions and identifying these are important for correct diagnosis and treatment selection. Clinical molecular imaging such as positron emission tomography can access several of these hallmarks of cancer non-invasively. Recently, hyperpolarized magnetic resonance spectroscopy with [1-${}^{13}$C] pyruvate has shown great potential to probe metabolic pathways. Here, we investigate simultaneous dual modality clinical molecular imaging of angiogenesis and deregulated energy metabolism in canine cancer patients. Canine cancer patients (n = 11) underwent simultaneous [${}^{68}$Ga]Ga-NODAGA-E[(cRGDyK)]${}_2$ (RGD) PET and hyperpolarized [1-${}^{13}$C]pyruvate-MRSI (hyperPET). Standardized uptake values and [1-${}^{13}$C]lactate to total ${}^{13}$C ratio were quantified and compared generally and voxel-wise. Ten out of 11 patients showed clear tumor uptake of [${}^{68}$Ga]Ga-NODAGA-RGD at both 20 and 60 min after injection, with an average SUV${}_{mean}$ of 1.36 ± 0.23 g/mL and 1.13 ± 0.21 g/mL, respectively. A similar pattern was seen for SUV${}_{max}$ values, which were 2.74 ± 0.41 g/mL and 2.37 ± 0.45 g/mL. The [1-${}^{13}$C]lactate generation followed patterns previously reported. We found no obvious pattern or consistent correlation between the two modalities. Voxel-wise tumor values of RGD uptake and lactate generation analysis revealed a tendency for each canine cancer patient to cluster in separated groups. We demonstrated combined imaging of [${}^{68}$Ga]Ga-NODAGA-RGD-PET for angiogenesis and hyperpolarized [1-${}^{13}$C]pyruvate-MRSI for probing energy metabolism. The results suggest that [${}^{68}$Ga]Ga-NODAGA-RGD-PET and [1-${}^{13}$C]pyruvate-MRSI may provide complementary information, indicating that hyperPET imaging of angiogenesis and energy metabolism is able to aid in cancer phenotyping, leading to improved therapy planning.