Here we report a novel approach to detect non-labeled cationic compounds, named modulated saturation transfer (MOST)-MRI, based on their effect of modulating the exchange rate of surrounding exchangeable protons. MOST-MRI was able to detect polyethylenimine (PEI600, M.W. = 600 Da), at a high sensitivity (μM or μg/mL range) through its quenching effects on surrounding fast-exchanging protons. In animals, MOST-MRI detected the tumor uptake of PEI600 that was injected intratumorally at a low dose (50 μg/kg b.w.), indicating the potential of MOST-MRI for label-free imaging guidance that is needed for the development and clinical translation of cationic gene delivery systems.
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