In Vivo Molecular Imaging of Breast Cancer Metabolic Heterogeneity Using [1-13C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen

Metabolic MRI using hyperpolarized (HP) [1-13C]pyruvate is promising for diagnostic medicine, allowing the study of cancer metabolism and early detection of therapy response. However, a possible widespread and routine use requires high-throughput and user-friendly technologies to produce the hyperpolarized media. Recently, we introduced a fast (6 min) and cost-effective method using Spin-Lock Induced Crossing and Signal Amplification By Reversible Exchange (SLIC-SABRE) at µT fields and a rapid purification to produce biocompatible HP solutions of aqueous pyruvate. In this study, we used SLIC-SABRE to conduct in vivo tumor metabolic imaging in a transgenic breast cancer mouse model (MMTV-PyMT). In agreement with previous HP MRI cancer studies, an elevated lactate metabolism was found in tumors compared to healthy breast tissue, heart, and vasculature, as well as distinct metabolic profiles within different tumor compartments. These findings suggest a potential link between lactate-to-pyruvate ratios and the varying levels of tumor cell proliferation and apoptosis observed by histological analyses. Our results underscore the potential of SABRE to enhance the accessibility and throughput of HP MRI, thereby advancing cancer research and diagnostic oncology.