(+/-) 3-(Ethoxycarbonyl)-2-imidazol-1-ylpropionic acid
3-(Ethoxycarbonyl)-2-imidazol-1-ylpropionic acid, abbreviated as IEPA, was the ﬁrst probe synthesized in our laboratories already in 1992, that made possible the non-invasive measurement of pHe in vivo tumors using 1H NMR Spectroscopic Imaging (1H MRSI). Multiple, localized, pHe measurements using this probe were conveniently obtained by determining the chemical shifts of its imidazolic H-2 proton in the collection of contiguous voxels provided by the 1H MRSI experiment. We selected the imidazole ring in the design of IEPA basically for two reasons: (i) the imidazole pKa (ca. 7.0) is very close to physiological pH allowing accurate pH measurements, and (ii) its H-2, H-4 and H-5 proton resonances are easily resolved and observed in the aromatic region of 1H NMR spectra, sufﬁciently far away from the water and the crowded aliphatic regions of the spectrum.
van Sluis R, Bhujwalla ZM, Raghunand N, et al. In vivo Imaging of Extracellular pH using 1H MRSI. Magn Res Med 1999;41:743–50.