title: AUR Memorial Award 1993. A drug system (PDH) for interventional radiology. Synthesis, properties, and efficacy.
abstract: OBJECTIVE
  The authors synthesized and tested a novel hydrogel system proposed for use in extra- and intravascular radiologic interventions, such as chemoembolizations and embolizations, and as a vehicle for sustained drug release.
  
  
  METHODS
  The material was specifically designed to meet the prerequisites of biodegradation, biocompatibility, low immunogenicity, low toxicity, and easy use. The material consists of a protein backbone cross-linked with activated bifunctional polyethyleneglycol (PEG) derivatives (PEG-derivatized hydrogel, [PDH]) to which are attached therapeutic (e.g., doxorubicin, a chemotherapeutic agent = PDH-dx) or diagnostic labels (e.g. Gd-DTPA).
  
  
  RESULTS
  PDH-dx effectively reduced the risk of local tumor recurrence in a rat model when implanted locally after surgical tumor removal. After administration, PDH is degraded by proteases release from macrophages; implantations of 1 mL samples into paraspinal muscles of rats were completely absorbed within 4 weeks and its constituents were metabolized. Antibody titers (total Ig response) against the PDH were not detectable 1 week after implantation, whereas protein control substances elicited a strong response.
  
  
  CONCLUSIONS
  PDH and its derivatives are relatively nontoxic, biodegradable materials for use in radiologic interventions and as a vehicle for sustained drug release.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston 02114.
authors.forename: R
authors.initials: R
authors.lastname: Weissleder
authors.forename: A
authors.initials: A
authors.lastname: Bogdanov
authors.forename: H
authors.initials: H
authors.lastname: Frank
authors.forename: N
authors.initials: N
authors.lastname: Nossiff
authors.forename: A
authors.initials: A
authors.lastname: Bogdanova
authors.forename: B K
authors.initials: BK
authors.lastname: Schaffer
authors.forename: T
authors.initials: T
authors.lastname: Brady
authors.forename: J
authors.initials: J
authors.lastname: Wittenberg
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental; D003432:Cross-Linking Reagents / Q000493:pharmacokinetics / Q000633:toxicity; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity; D016503:Drug Delivery Systems; D005782:Gels; D008279:Magnetic Resonance Imaging; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000473:pathology; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000633:toxicity; D015641:Radiography, Interventional; D051381:Rats; D011916:Rats, Inbred F344; D012235:Rhodamines / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D003432:Cross-Linking Reagents; D005782:Gels; D012235:Rhodamines; D011092:Polyethylene Glycols; D004317:Doxorubicin