Weissleder, R.Poss, K.Wilkinson, R.Zhou, C.Bogdanov, A. Jr2019-09-211995Weissleder, R, K Poss, R Wilkinson, C Zhou, and A Bogdanov, Jr. 1995. "Quantitation of slow drug release from an implantable and degradable gentamicin conjugate by in vivo magnetic resonance imaging." Antimicrobial Agents and Chemotherapy 39 (4): 839–845.0066-48041098-6596http://nrs.harvard.edu/urn-3:HUL.InstRepos:41384302A biodegradable model hydrogel containing a covalently bound aminoglycoside in which drug release can be monitored by magnetic resonance imaging (MRI) in vivo was developed, The hydrogel consists of the bis-hydroxysuccinimide ester of polyethylene glycol disuccinate cross-linked albumin, to which gentamicin and Gd-diethylenetriaminepentaacetic acid are covalently attached in stochiometric quantities. MRI allowed us to depict the three-dimensional structure of implanted gels, to accurately calculate their volumes, and thus to calculate the concentration of hydrogel-bound gentamicin. The correlation coefficient for the concentration of released gentamicin and the hydrogel volume was 0.965, Free and hydrogel-released gentamicin conjugates had similar antibiotic efficacies when tested in microbiological agar diffusion assays. In vivo, hydrogel-released gentamicin had a longer half-life in plasma than unaltered gentamicin (5.6 versus 0.7 h), presumably because of residual bound polyethylene glycol residues, Hydrogel implants into rats resulted in a prolonged (7 to 10 days) release of gentamicin and a decreased 24-h mortality in mice infected with a lethal dose of Pseudomonas aeruginosa. The results indicate the feasibility of imaging and quantitating therapeutic drug concentrations in vivo by MRI.en-USJournal Article2019-09-21