Multimodal elucidation of the Choline metabolism in a Murine Glioma model using magnetic resonance spectroscopy and 11C-choline positron emission tomography

The metabolites, transporters and enzymes involved in choline metabolism are regarded as biomarkers for disease progression in a variety of cancers, but their in vivo detection is not ideal. Both MR Spectroscopy (MRS using CSI tCho) and 11C-choline PET can probe this pathway, but they have not been compared side by side. In this study, we used the spontaneous murine astrocytoma model SMA560 injected intracranially injected into syngeneic VM/Dk mice, analyzing animals at various post-implantation time points using dynamic microPET imaging and chemical shift imaging MR spectroscopy. We observed an increase in tumor volume and 11C-choline uptake between days 5-18. Similarly, tCho levels decreased at days 5-18. We found a negative correlation between the tCho and PET results in the tumor and a positive correlation between the tCho tumor-to-brain ratio and choline uptake in the tumor. PCR results confirmed expected increases in expression levels for most of the transporters and enzymes. Using MRS quantification, a good agreement was found between CSI and 11C-choline PET data, while a negative correlation occurred when CSI was not referenced. Thus, 11C-choline PET and MRS methods appeared to be complementary in strengths. While advancing tumor proliferation caused an increasing 11C-choline uptake, gliosis and inflammation potentially accounted for a high peritumoral tCho signal in CSI, as supported by histology and secondary ion mass spectrometry (SIMS) imaging. Our findings provide definitive evidence of the utility of MRS, CSI and PET for imaging tumors in vivo.