Table 2.

Examples of hyperpolarized NMR probing.

Observable	Probe	References
(i) Designed probes
Amino acid concentrations	acetic anhydride	[39]
Binding	1H, 13C and 19F in binders	[42–44]
Drug metabolism	Carbamazepine	[46]
Ca2+ concentration	trimethylphenylammonium ubstituted with triacetic acid	[38]
Contrast agent	6LiCl	[63]
Enzyme activity	trimethylphenylammonium substituted with methyl ester	[38]
Hocl	p-Anisidine	[36]
Hydrogen peroxide	benzoylformic acid trimethylphenylammonium substituted with boronic acid ester	[38,64]
pH	89Y-complexes	[28,34]
Protein expression	N-acetyl-L-methionine	[49]
(ii) Derivatized endogenous probes
Enzyme activity	3,5-Difluorobenzoyl-L-glutamic acid (carboxypeptidase prodrug)	[48]
Enzyme activity	ethyl pyruvate	[57]
Perfusion	permethylated amino acids (betains)	[51]
Protein expression	pyruvate derivatives as reporter groups	[37]
(iii) Endogenous probes
Cell permeability, lysis	fumarate metabolism	[65]
	pyruvate diffusion	[66]
Drug efficacy	pyruvate	[67–69]
	fumarate	[65]
Enzyme activities and reaction fluxes
• Ldh	pyruvate, lactate	[70,71]
• Alt	alanine, pyruvate	[50]
• Bcat	ketoisocaproic acid	[72]
• Glutaminase	glutamine	[73,74]
• Carnitine acetyltransferase, AcetylCoA synthetase	acetate	[75]
• Betaine aldehyde metabolism	choline analog	[76]
• Pyruvate decarboxylase	pyruvate	[77]
• Pyruvate dehydrogenase	pyruvate	[78,79]
Enzyme mechanistic studies	fructose	[61]
	alanine	[80]
Gene expression, gene loss	glucose	[61,81]
Intracellular pH	acetate	[82]
	pyruvate	[83]
Metabolic strategies in different genomes	glucose	[61]
Oncogene signalling	pyruvate	[84]
	ketoisocaproic acid	[72]
Pathway activity, bottlenecks
• Glycolysis	glucose	[61,85–87]
• Indicator of aerobic glycolysis	[1-13C]pyruvate	[71,88,89]
• TCA cycle	[2-13C]pyruvate	[90]
• Fatty acid and ketone body metabolism	butyrate	[91]
Redox status	dehydroascorbic acid	[92,93]
Sulfite cytotoxicity	glucose	[94]
Tissue pH	bicarbonate	[95]
Transporter level and activity
•Glucose transporter	glucose	[86]
•Monocarboxylate transporter	pyruvate	[88,96]
•Urea carrier	urea	[97]
Tumor grading	alanine, pyruvate, lactate	[98]