The C-neu mammary carcinoma in Oncomice; characterization and monitoring response to treatment with herceptin by magnetic resonance methods.
To characterize spontaneously occurring c-neu/HER2 overexpressing tumours in oncomice and their response to herceptin by non-invasive magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). Oncomice were monitored by localized 31P MRS during unperturbed growth and before and after treatment with 10 mg/kg herceptin (Hoffman La Roche) intraperitoneally for up to 21 days post-treatment. Vascular morphology and function was assessed by quantitation of tumour magnetic resonance (MR) relaxation rates R2* and R2 prior to and either during carbogen (95% O2/5% CO2) breathing or following administration of the blood-pool contrast agent NC100150 (Clariscan, Amersham Health). Immunohistochemistry showed strong membrane staining for HER2 protein overexpression. The 31P MRS showed only a significant (p<0.01) increase of phosphomonoester / total phosphate ratio over 21 days of growth. Herceptin increased the tumour volume doubling time compared to untreated tumours and significantly increased the phosphomonoester / beta-nucleoside triphosphate ratio 2 days after treatment (p=0.01). Tumours showed a highly heterogeneous yet significant (p<0.01) decrease or increase in R2* in response to carbogen or NC100150 respectively. The absence of a decline in tumour bioenergetics with growth, commonly seen in 31P MRS studies of transplanted rodent tumour models, coupled with the heterogeneous blood volume revealed by 1H MRI, suggest a metabolic and vascular phenotype similar to that found in human tumours.
Rodrigues
L M
LM
CR UK Biomedical Magnetic Resonance Research Group, Department of Basic Medical Sciences, St. George's Hospital Medical School, London, SW17 0RE, UK. lrodrigu@sghms.ac.uk
Stubbs
M
M
Robinson
S P
SP
Newell
B
B
Mansi
J
J
Griffiths
J R
JR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018739:Oncogene Proteins v-erbB / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018739:Oncogene Proteins v-erbB; D000068878:Trastuzumab