Synthesis and testing of a p-H2 hyperpolarized 13C probe based on the pyrazolo[1,5-a]pyrimidineacetamide DPA-713, a MRI-vector to target the peripheral benzodiazepine receptors

DPA-713 is the lead compound of a recently developed 2-phenylpyrazolo[1,5-a]pyrimidineacetamide series that has been shown to display a good targeting capability toward peripheral benzodiazepine receptors, recently renamed translocator protein (18 kDa) or in short TSPO. On the basis of this structure, a novel derivative bearing a [13C]butynoate moiety has been designed and synthesized (three steps—42% overall yield) providing, upon rapid and quantitative para-hydrogenation, the corresponding hyperpolarized [13C]alkene. Para-hydrogen-induced polarization effects have been detected in both 1H and 13C-NMR spectra. Upon applying a field cycling procedure, the spin order of para-H2 added hydrogens is transferred on the 13 C carboxylate moiety yielding a signal enhancement of approximately 4500 times. T1 of the carboxylate carbon atom is approximately 21.9 s (at 9.37 T). A 13 C-MR image has been acquired by using the 13 C RARE (Rapid Acquisition by Relaxation Enhancement) acquisition protocol on a 10-mM solution. The main limitation to the in vivo use of this novel para-hydrogenated [13 C]derivative is its relatively low solubility in aqueous systems.