title: Magnetic resonance imaging-based prospective detection of intraperitoneal human ovarian carcinoma xenografts treatment response.
abstract: The feasibility of applying magnetic resonance imaging (MRI) for conducting prospective studies of intraperitoneal (i.p.) tumor treatment response to chemotherapy and resultant effects on survival in human ovarian carcinoma/nude mouse orthotopic xenograft models was evaluated. Female nude mice were implanted i.p. with either NMP-1 or SKOV-3ip. human ovarian carcinoma cells on day 0. Initial T2-weighted magnetic resonance (MR) images of the abdomens of NMP-1-implanted mice were obtained on day 7 to confirm the presence of nascent tumors; similar confirmations were made on day 14 with mice bearing SKOV-3ip. xenografts. On the initial imaging days, a multiple-dose regimen of cisplatin (CDDP; qd7 x3) was commenced, using 4 or 6 mg/kg treatments with the NMP-1 model and using 6 mg/kg treatments with the SKOV-3ip. model. Mice were reimaged multiple times, 2 days following each CDDP injection and at later times as well, depending on host survival. The images for each mouse from the last imaging day (day 30 for NMP-1, day 44 for SKOV-3ip.) were used in a blinded fashion to attempt to visually distinguish control from treated mice and to determine whether MRI could predict a survival benefit. For SKOV-3ip. mice, ten out of ten mice were correctly segregated into the control or the CDDP treatment group based solely on these blinded, nonquantified MR results. In this model, the 6 mg/kg multiple-dose regimen achieved a modest response, improving life span by approximately 24%. However, for the NMP-1 mice, only six out of nine evaluable mice were correctly segregated into the control or one of the treatment groups by similar MRI criteria, a virtually random distribution; further, neither CDDP treatment regimen achieved a significant improvement in survival in this model. In another study, NMP-1-implanted mice were treated on day 7 after tumor implantation with a single injection of a hyaluronic acid-paclitaxel copolymer. Control and treated mice were MR imaged on day 28, which revealed marked reductions in tumor burden in treated mice, correlating well with a subsequently observed improved survival of approximately 40%. Our results suggest that MRI can be used to serially and noninvasively monitor treatment response and predict ongoing treatment effects on survival.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA. jkloster@mdanderson.org
authors.forename: J
authors.initials: J
authors.lastname: Klostergaard
authors.forename: E
authors.initials: E
authors.lastname: Auzenne
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.forename: D
authors.initials: D
authors.lastname: Farquhar
authors.forename: B
authors.initials: B
authors.lastname: Rivera
authors.forename: R E
authors.initials: RE
authors.lastname: Price
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D051379:Mice; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use*; D010534:Peritoneal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000556:secondary; D011108:Polymers / Q000627:therapeutic use; D011237:Predictive Value of Tests; D016037:Single-Blind Method; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D006820:Hyaluronic Acid; D017239:Paclitaxel; D002945:Cisplatin