title: Biodistribution and pharmacokinetics of the (19)F-labeled radiosensitizer 3-aminobenzamide: assessment by (19)F MR imaging.
abstract: 3-Aminobenzamide (3-ABA) is a potent radiosensitizer that inhibits the repair of DNA strand breaks. The aim of this study was to monitor the biodistribution and pharmacokinetics of a fluorinated 3-ABA derivative in tumor-bearing rats by magnetic resonance imaging (MRI). To this end, 3-ABA was labeled with fluorine-19 by trifluoroethylation [3-amino-N-2,2,2-trifluoroethylbenzamide (3-ABA-TFE)], which only slightly increased the cytotoxicity of the compound as demonstrated by colony-forming assays. After intraperitoneal injection of 400 mg/kg BW 3-ABA-TFE to nine Copenhagen rats with Dunning prostate adenocarcinoma, (19)F MR images were acquired at a whole-body MR system with a spatial sampling of 10 x 10 x 15 mm(3). While 3-ABA-TFE was observed in all major organs and the muscular system, only a small and heterogeneous signal could be detected in the adenocarcinoma. Serial MR measurements yielded maximum tissue signals about 2 days after 3-ABA-TFE administration. At this time point, the mean muscle-to-liver and tumor-to-liver signal ratio was 0.31+/-0.07 and 0.11+/-0.04, respectively. Application of the (19)F MRI strategy makes it possible to measure the biodistribution and pharmacokinetics of 3-ABA-TFE in individual animals in a longitudinal manner. The results obtained for the prostate adenocarcinoma indicate that delivery of 3-ABA-TFE to solid tumors may be seriously hampered by tumor-specific factors and that the intratumoral uptake of the substance may be lower than in normal tissues. Therefore, the development of effective carrier systems is mandatory to improve tumor-selective delivery.
authors.affiliation: Research Program 'Innovative Diagnosis and Therapy,' German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brix
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schlicker
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.forename: Peter
authors.initials: P
authors.lastname: Peschke
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Bellemann
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000532:radiotherapy; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D001549:Benzamides; D005462:Fluorine Radioisotopes; D011838:Radiation-Sensitizing Agents; C025160:3-aminobenzamide