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The C-neu mammary carcinoma in Oncomice; characterization and monitoring response to treatment with herceptin by magnetic resonance methods

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Abstract

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 / β-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.

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Acknowledgments.

This work was supported by the Cancer Research UK Grant No. C12/A1209. SPR is a recipient of a Royal Society University Research Fellowship. The authors would like to thank Roche Products PLC for the supply of herceptin and Glyn Fisher and his staff at St. George’s Hospital Medical School for care of the animals.

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Authors and Affiliations

  1. CR UK Biomedical Magnetic Resonance Research Group, Department of Basic Medical Sciences, St. George’s Hospital Medical School, London, SW17 0RE, UK

    L. M. Rodrigues, M. Stubbs, S. P. Robinson & J. R. Griffiths

  2. Farnborough Hospital, Farnborough Common, Orpington, Kent, BR6 8ND, UK

    B. Newell

  3. Department of Cellular and Molecular Medicine, St. George’s Hospital Medical School, London, SW17 0RE, UK

    J. Mansi

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  1. L. M. Rodrigues
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  2. M. Stubbs
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  6. J. R. Griffiths
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Correspondence to L. M. Rodrigues.

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Rodrigues, L., Stubbs, M., Robinson, S. et al. The C-neu mammary carcinoma in Oncomice; characterization and monitoring response to treatment with herceptin by magnetic resonance methods. MAGMA 17, 260–270 (2004). https://doi.org/10.1007/s10334-004-0070-8

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  • DOI: https://doi.org/10.1007/s10334-004-0070-8

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