title: Synthesis and characterization of HE-24.8: a polymeric contrast agent for magnetic resonance angiography.
abstract: The physical and biological properties of a water-soluble polymeric contrast agent based on a complex of N-(2-hydroxypropyl)methacrylamide copolymer with gadolinium (HE-24.8) were investigated, and its potential for experimental magnetic resonance (MR) angiography was assessed. Relaxivities of Gd-DTPA-BMA, Gd-DTPA-HSA (human serum albumin), and HE-24.8 were determined at 1.5 T. Thermic stability and biocompatibility of HE-24.8 were assessed in vitro and by analyzing kinetics and organ distribution in rats for up to 2 weeks. For comparison, HE-24.8- and Gd-DTPA-HSA-enhanced micro-MR angiographies of brain, chest, and subcutaneous tumors in rats were performed. T1 relaxivity of HE-24.8 (21.3 +/- 1.1 mM(-1) s(-1)) was 5-fold higher than that of Gd-DTPA-BMA (4.1 +/- 0.1 mM(-1) s(-1)) and twice as high as that of Gd-DTPA-HSA (12.4 +/- 0.2 mM(-1) s(-1)). Varying the molecular weight of the polymer (15-46 kDa) did not significantly change the T1 relaxivity. In rats, 20 and 10% of the injected dose of HE-24.8 was detected at 24 and 168 h postinjection, respectively. Upon a relatively rapid initial renal clearance, no specific retention in any organ was noted, with some exception for the reticulo-endothelial system. No measurable release of gadolinium from the polymer-Gd complex or cell toxicity was observed during its incubation in aqueous environment. Excellent display of rat and tumor vascularization was achieved with Gd-DTPA-HSA and HE-24.8; however, contrast of vessels was higher in HE-24.8-enhanced scans. HE-24.8 is considered a macromolecular contrast agent highly suited for experimental MR studies.
authors.affiliation: Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany. F.Kiessling@dkfz.de
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.forename: Melanie
authors.initials: M
authors.lastname: Heilmann
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.forename: Karel
authors.initials: K
authors.lastname: Ulbrich
authors.forename: Vladimir
authors.initials: V
authors.lastname: Subr
authors.forename: Peter
authors.initials: P
authors.lastname: Peschke
authors.forename: Bjoern
authors.initials: B
authors.lastname: Waengler
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.forename: Hans-Herrmann
authors.initials: HH
authors.lastname: Schrenk
authors.forename: Michael
authors.initials: M
authors.lastname: Bock
authors.forename: Lothar
authors.initials: L
authors.lastname: Schad
authors.forename: Wolfhard
authors.initials: W
authors.lastname: Semmler
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003287:Contrast Media / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism; D051381:Rats
chemical_list: D003287:Contrast Media; C513574:HE-24.8 gadolinium; D009942:Organometallic Compounds; D011109:Polymethacrylic Acids; C011533:Duxon; D005682:Gadolinium