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Abstract:
Magnetic resonance imaging (MRI) is a powerful tool in clinical diagnostics and is also used for the understanding of developmental and biological processes. It visualizes the differences in tissues and organs, as well as between normal and pathological states. Due to its noninvasive nature, excellent spatial resolution and tissue penetration, MRI became one of the preferential methods for molecular and cellular imaging. The specificity and sensitivity of MRI can be further enhanced by the introduction of contrast agents. Many of the currently existing contrast agents are restricted to the extracellular space, though novel approaches enforce generations of intracellular contrast agents that can be developed for targeted labeling of cells for the visualization of a specific biological process. However, the lower sensitivity of MRI as compared to other imaging techniques demands certain quantitative considerations for the rational design of these intracellular agents. Gadolinium complexes are the most frequent choice for T1-weigthed MR-imaging. Besides having a high longitudinal relaxivity (r1), these agents should also be delivered in a sufficient amount to target structures on the cell membrane or inside the cells. We have performed a study in an attempt to determine the minimum number of gadolinium ions needed for the efficient labeling of cells. The concentration dependent contrast enhancement of Gd-DOTA, Gd-DO3A or Gd-AAZTA in T1-weighted MR-images of phantoms with water only, cell culture medium containing serum, or in the presence of cells was followed at different, ultra-high magnetic fields (3T, 7T, 16.4T) and with the spatial resolution commonly used for in vivo measurements. The results suggest MRI detectability at low micromolar concentrations for all applied contrast agents, which correspond to the previously predicted number of metal atoms per cell [1]. However, this number is dependent on the r1 of the contrast agent and the magnetic field of the imaging scanner. Financial support of the Max-Planck Society and German Ministry for Education and Research (BMBF, FKZ: 01EZ0813) is gratefully acknowledged.
