Table 2.

List of ¹³C DNP probes that have been polarized and MR sequences applied to the study of altered metabolic pathways in low-grade mutant IDH1 glioma orthotopic model and cells.

	Altered Pathways	REF	HP 13C MRS
			HP Probe	Sequences	Use	REF
Low-grade mutant IDH1 glioma	Alterations linked to 2-HG accumulation ✓↑ 2-HG ✓↓ BCAT1, AST1/2, GDH1/2 activities ✓LDHA silencing ✓↓ PDH ✓↓ MCT1 and MCT4	10, 42, 56–58, 79	[1-13C]-α-KG T1~52s at 9.4T Php~16%	In vivo: ✓Multiband spectral-spatial RF pulse with variable flip angle In cells: ✓dynamic non localized acquisition with low flip angle	Conversion to [1-13C]-2-HG: ↑ both in cells and in an orthotopic glioma model harboring IDH1 mutation Conversion to [1-13C]-glutamate: ↓ in an orthotopic U87 glioma harboring IDH1 mutation	62, 78,79
			[1-13C]-pyruvate T1~67s at 3T Php~14–40%	In vivo: ✓dynamic 2D CSI with low flip angle In cells: ✓dynamic non localized acquisition with low flip angle	Conversion to [1-13C]-lactate: ✓low production in an orthotopic tumor model ✓↓ in cells harboring IDH1 mutation as compared to the IDH1 wild-type cells	69, 57
			[2-13C]-pyruvate T1~40s at 3T Php~27%	In cells: ✓dynamic non localized acquisition with low flip angle	Conversion to [2-13C]-lactate ✓↑ in U87 and NHAs cells ✓↓ following DCA treatment in same cell models Conversion to [5-13C]-glutamate ✓↓ in U87 and NHAs cells ✓↑ following DCA treatment in same cell models	30, 77
			[1-13C]-ethyl pyruvate T1~45s at 3T Php~28–35%		Not yet applied to the study of low-grade brain tumor	81
			[U-13C]-α-KB T1~52s at 3T Php~10%		Not yet applied to the study of low-grade brain tumor	82
	Elevated levels of ROS linked to reduce activity of wild-type IDH ✓↓ NADPH ✓↓ glutathione	59	[1-13C]-dihydroascorbate T1~57s at 3T Php ~6–8%		Conversion to [1-13C]-vitamin C illustrated in normal rat brain Not yet applied to the study of brain cancer	88, 89
	Abnormal choline metabolism associated with IDH1 mutation ✓↓ PC ✓↑ GPC	43, 53–55	[2-13C, 1,22H4]-choline chloride T1~60s at 3T Php~28–35%		Not yet applied to the study of low-grade brain tumor	101–103
	Necrosis: increase permeability of the necrotic cell membrane ✓↑ uptake fumarate ✓↑ release fumarase enzyme	98–100	[1,4-13C2]-fumarate T1~24s at 9.4T Php ~26–35%		Not yet applied to the study of GBM	98–100