title: Application of arsenazo III in the preparation and characterization of an albumin-linked, gadolinium-based macromolecular magnetic resonance contrast agent.
abstract: A macromolecular magnetic resonance contrast agent (MMCA) was prepared by linking bovine serum albumin (BSA) to gadolinium (Gd) via a chelating agent, diethylenetriaminepentaacetic acid (DTPA). Colorimetric testing with 2,7-bis(o-arsenophenylazo)-1,8-dihydroxynaphthalene-3,6-disulfonic acid (arsenazo III) was performed to check for the appearance of free gadolinium during preparation and to quantify the Gd content in the final product. The complex was purified by dialysis, concentrated by lyophilyzation and characterized by magnetic resonance (MR) proton relaxation times. The resultant product had a molecular weight of about 90 kDa, Gd:BSA ratio of 14:1, and T1 and T2 relaxation times of 128.3 and 48.9 ms, respectively, at a field strength of 7Tesla (T) and at 20% concentration. Contrast enhancement of Gadomer-17 (a dendritic MMCA) and Gd-linked to BSA (Gd-BSA) was sequentially evaluated in a rat brain gliosarcoma model (n = 5) by MR imaging (MRI). Following intravenous injection, the blood concentration of Gadomer-17 fell rapidly, whereas that of Gd-BSA was almost constant for the duration of imaging. The areas of enhancement of both MMCAs were comparable. The spatial distribution of Gd-BSA showed good agreement with Evans blue-tagged albumin. Treatment with dexamethasone decreased Gd-BSA enhancement in the tumor. These results suggest that the arsenazo III method is applicable in preparing Gd-BSA to image brain tumors and their response to treatment. This simple method may also be useful for preparing other gadolinium-linked MMCAs.
authors.affiliation: Department of Anesthesiology, Henry Ford Health System, Detroit, MI 48202, USA. annta@neuro.hfh.edu
authors.forename: Tavarekere N
authors.initials: TN
authors.lastname: Nagaraja
authors.forename: Richard L
authors.initials: RL
authors.lastname: Croxen
authors.forename: Swayamprava
authors.initials: S
authors.lastname: Panda
authors.forename: Robert A
authors.initials: RA
authors.lastname: Knight
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Keenan
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Brown
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fenstermacher
authors.forename: James R
authors.initials: JR
authors.lastname: Ewing
mesh_terms: D000818:Animals; D001150:Arsenazo III / Q000737:chemistry*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D005682:Gadolinium / Q000032:analysis* / Q000737:chemistry; D018316:Gliosarcoma / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D011877:Radionuclide Imaging; D051381:Rats; D011916:Rats, Inbred F344; D012710:Serum Albumin, Bovine / Q000737:chemistry*
chemical_list: D003287:Contrast Media; C058230:gadolinium-bovine serum albumin complex; D001150:Arsenazo III; D012710:Serum Albumin, Bovine; D005682:Gadolinium