title: Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation.
abstract: Permeability of tumor vasculature can be a major barrier to successful drug delivery, particularly for high molecular weight agents such as monoclonal antibodies and their diagnostic or therapeutic conjugates. In this study, changes in permeability of SCCVII tumor vessels after radiation treatment were evaluated by dynamic magnetic resonance imaging as a function of time after irradiation using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance imaging contrast agent shown previously to be confined to tumor blood vessels. Tumor irradiation consisted of either single doses (2-15 Gy) or various daily fractionated doses (5 days). A single radiation dose of 15 Gy resulted in significant transient image enhancement of the tumor tissue with a maximum occurring between 7 and 24 hours after radiation treatment. No observable enhancement was recorded for fractionated radiation doses. Use of dynamic magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology capable of defining the timing of enhanced permeability of macromolecules in tumors after irradiation. Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies.
authors.affiliation: Metabolism Branch, Radiation Biology Branch, and Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1002, USA. kobayash@mail.nih.gov
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Koen
authors.initials: K
authors.lastname: Reijnders
authors.forename: Sean
authors.initials: S
authors.lastname: English
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Yordanov
authors.forename: Diane E
authors.initials: DE
authors.lastname: Milenic
authors.forename: Anastasia L
authors.initials: AL
authors.lastname: Sowers
authors.forename: Deborah
authors.initials: D
authors.lastname: Citrin
authors.forename: Murali C
authors.initials: MC
authors.lastname: Krishna
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000588:Amines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003287:Contrast Media / Q000494:pharmacology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D046911:Macromolecular Substances / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply*; D009381:Neoplasms, Radiation-Induced / Q000473:pathology*; D009389:Neovascularization, Pathologic; D009757:Nylons / Q000737:chemistry* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000588:Amines; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D003287:Contrast Media; D046911:Macromolecular Substances; D009757:Nylons