Assessment of anti-metastatic drug efficacy via localization and quantification of ex vivo murine bone tumor load using high-throughput MRI T1 parametric analysis.
MRI methods show great utility for assessing the growth of tumors metastasized to bone in clinical studies. However, preclinical MRI methods in rodents do not translate well to high-throughput studies of bone tumors, especially for early-stage tumors typically examined in pharmaceutical discovery efforts. To overcome these limitations, an ex vivo MR T1 parametric mapping method has been developed to measure metastasized bone tumor load in murine long bones. This method has been used to assess the therapeutic efficacy of SU11248, a multi-targeted inhibitor with demonstrated anti-tumor activity and reduction of bone loss, in a murine model of metastasized breast tumor cells. The results show precise localizations of relative tumor loads within the bones and reveal significant differences between SU11248-treated and untreated animal groups. The procedures were optimized for simultaneous, high-throughput parallel image acquisition of MRI data for 30 samples and included an automated segmentation method for image processing. The merits of this T1 parametric mapping method are compared with clinical T1-weighted MRI methods, histopathology and bioluminescence imaging of the same murine bone tumor model.
Pagel
Marty D
MD
Pharmacia Corporation, 700 Chesterfield Parkway West, St. Louis, MO 63017, USA. mpagel@case.edu
Baldwin
Steven J
SJ
Rader
Randall K
RK
Kotyk
John J
JJ
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000556:secondary*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000556:secondary; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007211:Indoles / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib