Magnetic resonance imaging-based prospective detection of intraperitoneal human ovarian carcinoma xenografts treatment response.
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.
Klostergaard
J
J
Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA. jkloster@mdanderson.org
Auzenne
E
E
Ghosh
S
S
Farquhar
D
D
Rivera
B
B
Price
R E
RE
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
D000970:Antineoplastic Agents; D011108:Polymers; D006820:Hyaluronic Acid; D017239:Paclitaxel; D002945:Cisplatin