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 (31)p 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 R-2* and R-2 prior to and either during carbogen (95% O-2/5% CO2) breathing or following administration of the blood-pool contrast agent NC100150 (Clariscan, Amersham Health). lmmunohistochemistry showed strong membrane staining for HER2 protein overexpression. The P-31 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 P-31 MRS studies of transplanted rodent tumour models, coupled with the heterogeneous blood volume revealed by 1 H MRI, suggest a metabolic and vascular phenotype similar to that found in human tumours.