Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
Graduate Program in Bioengineering, University of California, Berkeley and San Francisco, San Francisco, California, USA.
Magn Reson Med. 2022 Jan;87(1):138-149. doi: 10.1002/mrm.28965. Epub 2021 Aug 10.
The combined hyperpolarized (HP) C pyruvate and urea MRI has provided a simultaneous assessment of glycolytic metabolism and tissue perfusion for improved cancer diagnosis and therapeutic evaluation in preclinical studies. This work aims to translate this dual-probe HP imaging technique to clinical research.
A co-polarization system was developed where [1- C]pyruvic acid (PA) and [ C, N ]urea in water solution were homogeneously mixed and polarized on a 5T SPINlab system. Physical and chemical characterizations and toxicology studies of the combined probe were performed. Simultaneous metabolic and perfusion imaging was performed on a 3T clinical MR scanner by alternatively applying a multi-slice 2D spiral sequence for [1- C]pyruvate and its downstream metabolites and a 3D balanced steady-state free precession (bSSFP) sequence for [ C, N ]urea.
The combined PA/urea probe has a glass-formation ability similar to neat PA and can generate nearly 40% liquid-state C polarization for both pyruvate and urea in 3-4 h. A standard operating procedure for routine on-site production was developed and validated to produce 40 mL injection product of approximately 150 mM pyruvate and 35 mM urea. The toxicology study demonstrated the safety profile of the combined probe. Dynamic metabolite-specific imaging of [1- C]pyruvate, [1- C]lactate, [1- C]alanine, and [ C, N ]urea was achieved with adequate spatial (2.6 mm × 2.6 mm) and temporal resolution (4.2 s), and urea images showed reduced off-resonance artifacts due to the J coupling.
The reported technical development and translational studies will lead to the first-in-human dual-agent HP MRI study and mark the clinical translation of the first HP C MRI probe after pyruvate.
联合超极化（HP） 1- C 丙酮酸和尿素 MRI 为临床前研究中的癌症诊断和治疗评估提供了同时评估糖酵解代谢和组织灌注的方法。本研究旨在将这种双探针 HP 成像技术转化为临床研究。
开发了一种共极化系统，在 5T SPINlab 系统上将 [1- C]丙酮酸（PA）和水相中的 [ C, N ]尿素均匀混合并极化。对组合探针进行物理化学特性和毒理学研究。通过交替应用多切片 2D 螺旋序列对 [1- C]丙酮酸及其下游代谢物和 3D 平衡稳态自由进动（bSSFP）序列对 [ C, N ]尿素，在 3T 临床磁共振扫描仪上进行同时代谢和灌注成像。
联合 PA/尿素探针具有类似于纯 PA 的成玻璃能力，并且可以在 3-4 小时内在丙酮酸和尿素中产生近 40%的液态 C 极化。开发并验证了一种标准操作规程，用于现场常规生产，可生产约 150mM 丙酮酸和 35mM 尿素的 40mL 注射产品。毒理学研究表明了联合探针的安全性。通过 [1- C]丙酮酸、[1- C]乳酸、[1- C]丙氨酸和 [ C, N ]尿素的动态代谢物特异性成像，实现了足够的空间（2.6mm×2.6mm）和时间分辨率（4.2s），并且由于 J 耦合，尿素图像显示出减少的离共振伪影。
报告的技术发展和转化研究将导致首例人体双探剂 HP MRI 研究，并标志着继丙酮酸之后首个 HP 13C MRI 探针的临床转化。
