An Efficient T ₁ Contrast Agent for Labeling and Tracking Human Embryonic Stem Cells on MRI

Noninvasive cell tracking in vivo has the potential to advance stem cell-based therapies into the clinic. Magnetic resonance imaging (MRI) provides an excellent image-guidance platform; however, existing MR cell labeling agents are fraught with limited specificity. To address this unmet need, we developed a highly efficient manganese porphyrin contrast agent, MnEtP, using a two-step synthesis. In vitro MRI at 3 Tesla on human embryonic stem cells (hESCs) demonstrated high labeling efficiency at a very low dose of 10 µM MnEtP, resulting in a four-fold lower T ₁ relaxation time. This extraordinarily low dose is ideal for labeling large cell numbers required for large animals and humans. Cell viability and differentiation capacity were unaffected. Cellular manganese quantification corroborated MRI findings, and the agent localized primarily on the cell membrane. In vivo MRI of transplanted hESCs in a rat demonstrated excellent sensitivity and specificity of MnEtP for noninvasive stem cell tracking.