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To monitor the release of fluorinated drugs from polymeric carriers, a novel 19 F MRI enzyme-responsive contrast agent was developed and tested. This contrast agent was prepared by conjugation of 5-fluorouracil (5-FU) to hyperbranched poly( N , N -dimethylacrylamide) (HB-PDMA) via an enzyme-degradable peptide linker. Due to the different molecular sizes, the release of 5-FU from the 5-FU polymer conjugate resulted in a sufficiently substantial difference in spin-spin T  2  19 F NMR/MRI relaxation time that enabled differentiating between attached and released drug states. The 5-FU polymer conjugate exhibited a broad signal and short T  2 relaxation time under 19 F NMR analysis. Incubation with the enzyme induced the release of 5-FU, accompanied by an extension of T  2 relaxation times and an enhancement in the 19 F MRI signal. This approach is promising for application in the convenient monitoring of 5-FU drug release and can be used to monitor the release of other fluorinated drugs.

Synthesis of 5-Fluorouracil Polymer Conjugate and 19F NMR Analysis of Drug Release for MRI Monitoring