ParaHydrogen induced polarization (PHIP) is an efficient and cost-effective hyperpolarization method, but its application to biological investigations has been hampered, so far, due to chemical challenges. PHIP is obtained by means of the addition of hydrogen, enriched in the para-spin isomer, to an unsaturated substrate. Both hydrogen atoms must be transferred to the same substrate, in a pairwise manner, by a suitable hydrogenation catalyst; therefore, a de-hydrogenated precursor of the target molecule is necessary. This has strongly limited the number of parahydrogen polarized substrates. The non-hydrogenative approach brilliantly circumvents this central issue, but has not been translated to in-vivo yet. Recent advancements in hydrogenative PHIP (h-PHIP) considerably widened the possibility to hyperpolarize metabolites and, in this review, we will focus on substrates that have been obtained by means of this method and used in vivo. Attention will also be paid to the requirements that must be met and on the issues that have still to be tackled to obtain further improvements and to push PHIP substrates in biological applications.

副氢诱导极化 (PHIP) 是一种高效且具有成本效益的超极化方法，但迄今为止，由于化学挑战，其在生物研究中的应用受到阻碍。PHIP 是通过向不饱和底物添加富含对旋旋异构体的氢而获得的。两个氢原子必须通过合适的氢化催化剂以成对的方式转移到相同的底物上；因此，目标分子的脱氢前体是必要的。这极大地限制了仲氢极化底物的数量。非氢化方法巧妙地规避了这一核心问题，但尚未转化为体内方法。氢化 PHIP (h-PHIP) 的最新进展大大拓宽了超极化代谢物的可能性，在这篇综述中，我们将重点介绍通过这种方法获得并在体内使用的底物。还将关注必须满足的要求以及仍需解决的问题，以获得进一步的改进并推动 PHIP 底物在生物应用中的应用。