The interplay of T1- and T2-relaxation on T1-weighted MRI of hMSCs induced by Gd-DOTA-peptides

Three Gd-DOTA-peptide complexes with different peptide sequence are synthesized and used as T₁ contrast agent to label human mesenchymal stem cells (hMSCs) for magnetic resonance imaging study. The peptides include a universal cell penetrating peptide TAT, a linear MSC-specific peptide EM7, and a cyclic MSC-specific peptide CC9. A significant difference in labeling efficacy is observed between the Gd-DOTA-peptides as well as a control Dotarem. All Gd-DOTA-peptides as well as Dotarem induce significant increase in T₁ relaxation rate which is in favor of T₁-weighted MR imaging. Gd-DOTA-CC9 yields the maximum labeling efficacy but poor T₁ contrast enhancement. Gd-DOTA-EM7 yields the minimum labeling efficacy but better T₁ contrast enhancement. Gd-DOTA-TAT yields a similar labeling efficacy as Gd-DOTA-CC9 and similar T₁ contrast enhancement as Gd-DOTA-EM7. The underlying mechanism that governs T₁ contrast enhancement effect is discussed. Our results suggest that T₁ contrast enhancement induced by Gd-DOTA-peptides depends not only on the introduced cellular Gd content, but more importantly on the effect that Gd-DOTA-peptides exert on the T₁-relaxation and T₂-relaxation processes/rates. Both T₁ and particularly T₂ relaxation rate have to be taken into account to interpret T₁ contrast enhancement. In addition, the interpretation has to be based on cellular instead of aqueous longitudinal and transverse relaxivities of Gd-DOTA-peptides.