Dicarboxylic acids as pH sensors for hyperpolarized¹³C magnetic resonance spectroscopic imaging

Abstract

Imaging tumoral pH may help characterize aggressiveness, metastasis, and therapeutic response. We report the development of hyperpolarized [2–13C,D10]diethylmalonic acid, which exhibits a large pH-dependent 13C chemical shift over the physiologic range. We demonstrate that co-polarization with [1–13C,D9]tert-butanol accurately measures pH via 13C NMR and magnetic resonance spectroscopic imaging in phantoms.

Amino Acid‐Derived Sensors for Specific Zn2+ Detection Using Hyperpolarized 13C Magnetic Resonance Spectroscopy

“…It is worth noting that the [1‐ 13 C 2 ]IDA:Zn complex appears as two separate peaks while the [1‐ 13 C]Cys:Zn complex appears as a single peak, indicating that the on and off rates for [1‐ 13 C 2 ]IDA are slower than the frequency difference between bound and unbound resonances and the on and off rates for [1‐ 13 C]Cys are more rapid. These results are analogous to prior findings in 15 N, 19 F, and hyperpolarized 13 C pH imaging probe development efforts . Overall, these data demonstrate that the chemical shift of the [1‐ 13 C] NMR signal of cysteine and IDA change in a predictable and quantitative manner in response to Zn 2+ concentration.…”

Accurate pH Sensing using Hyperpolarized 129Xe NMR Spectroscopy

“…Also, Korenchan et al. monitored the 13 C chemical shift variation of DNP‐hyperpolarized [2‐ 13 C,D10]diethylmalonic acid (DEMA) with pH . NMR pH sensing with SABRE‐hyperpolarized 15 N imidazole used the 15 N chemical shift difference between the protonated and deprotonated forms of the molecule .…”

Imaging of Extracellular pH Using Hyperpolarized Molecules

“…13 C‐labelled dicarboxylic acids and molecules of the Good's buffers family have been shown to be pH‐sensitive in vitro . [2‐ 13 C]diethylmalonic acid ( 5 ) and [1‐ 13 C]N‐(2‐acetamido)‐2‐aminoethanesulfonic acid (ACES, 6 ) were used to generate pH images of buffered phantoms in MRI scanners.…”

“…In case dipolar coupling between high‐ γ nuclei ( 1 H) and heteronuclei is inevitable, deuterium enrichment is a feasible strategy to prolong T 1 , which was demonstrated for hyperpolarized molecules, such as choline, glucose and pyruvate. So far, pH‐sensitive dicarboxylic acids, e.g. ( 5 ), have been deuterated and thus exhibit long T 1 values of >1 min even at high field strength ( B 0 =11 T) .…”