Table 1.

Review of 13C-labeled probes employed in interrogating different metabolic pathways in pancreatic cancer systems.

HPa probe	Biochemical reaction	T1b of HP probe (seconds)	Quantification	Biological significance	References
[1-13C] Pyruvate	Pyruvate to lactate (catalyzed by LDHc); pyruvate to alanine (catalyzed by ALTd)	44-67	Rate constant of pyruvate to lactate (or alanine) or time-integrated ratio of lactate (or alanine)-to-pyruvate signals	Increased pyruvate-to-lactate flux is an indicator of the Warburg effect; total flux from pyruvate to (lactate+alanine) could be a measure of anaerobic glucose metabolism	Viale et al [17], Rao et al [22], Halbrook and Lyssiotis [49], Dutta et al [50]
[5-13C] or [5-13C-4-2H2] glutamine	Glutamine to glutamate (catalyzed by glutaminase)	16-30	Time-integrated ratio of glutamate-to-glutamine signals	Indicator of glutamine addiction as a characteristic of certain cancers; also a measure of α-ketoglutarate metabolism (glutamate converts to α- ketoglutarate and can feed the TCAe cycle).	Son et al [51]
[H13CO3–] bicarbonate	Bicarbonate to carbon dioxide	10-20	Using the relative concentrations of bicarbonate and carbon dioxide, apply the Henderson-Hasselbalch equation to calculate the tissue pH	The bicarbonate buffer system controls tissue pH; greater acidity of the tumor microenvironment has been linked to treatment resistance	Cruz-Monserrate et al [52], Gallagher et al [53]
[1,5-13C2] zymonic acid	N/Af	43-51	Chemical shift difference based on pH measurement	This is an organic moiety with no significant biological importance	Rao et al [21]
[1,4-13C2] fumarate	Fumarate to malate (cytosolic washout after cell necrosis)	~30	Malate signal is proportional to the amount of cell death	Fumarase (FH) enzyme is present in the cytosol and mitochondria of viable cells. Since cells cannot uptake fumarate, any HP malate production is a direct result of injected HP fumarate interacting with FH in the extracellular space, which has leaked out of necrotic cells; thus, it can be used to differentiate necrotic from viable cells	Silvers et al [54], Lee et al [55]
[1-13C] dehydroascorbate (DHA)	DHA/ascorbate cycle, GSHg/GSSGh cycle, and NAPDHi to NADP+	>50	Ratio of time-integrated ascorbate-to-DHA signal	Greater flux from DHA to ascorbate indicates less redox stress inside the cell; this is also an indirect measure of the GSSG-to-GSH ratio and NADPH metabolism	Lai et al [56], Salamanca-Cardona et al [57], Keshari et al [58-60]
[1-13C] α-keto isocaproate (α-KIC)	α-KIC to leucine (catalyzed by BCATj)	100	Ratio of time-integrated leucine-to-α-KIC signals	Indicator of BCAT level, which is upregulated in certain cancers	Wilson et al [61]

^aHP: hyperpolarization.

^bT₁: longitudinal relaxation time.

^cLDH: lactate dehydrogenase.

^dALT: alanine transaminase.

^eTCA: tricarboxylic acid cycle.

^fN/A: not applicable.

^gGSH: reduced glutathione.

^hGSSG: glutathione disulfide.

ⁱNAPDH: nicotinamide adenine dinucleotide phosphate.

^JBCAT: branched-chain aminotransferase.