Daniel W Mundy et al 2006 Phys. Med. Biol. 51 1377 doi:10.1088/0031-9155/51/6/001
Daniel W Mundy1, Wael Harb2 and Tatjana Jevremovic1
Show affiliationsA novel radiation targeted therapy is investigated for HER-2 positive breast cancers. The proposed concept combines two known approaches, but never used together for the treatment of advanced, relapsed or metastasized HER-2 positive breast cancers. The proposed radiation binary targeted concept is based on the anti HER-2 monoclonal antibodies (MABs) that would be used as vehicles to transport the nontoxic agent to cancer cells. The anti HER-2 MABs have been successful in targeting HER-2 positive breast cancers with high affinity. The proposed concept would utilize a neutral nontoxic boron-10 predicting that anti HER-2 MABs would assure its selective delivery to cancer cells. MABs against HER-2 have been a widely researched strategy in the clinical setting. The most promising antibody is Trastuzumab (Herceptin®). Targeting HER-2 with the MAB Trastuzumab has been proven to be a successful strategy in inducing tumour regression and improving patient survival. Unfortunately, these tumours become resistant and afflicted women succumb to breast cancer. In the proposed concept, when the tumour region is loaded with boron-10 it is irradiated with neutrons (treatment used for head and neck cancers, melanoma and glioblastoma for over 40 years in Japan and Europe). The irradiation process takes less than an hour producing minimal side effects. This paper summarizes our recent theoretical assessments of radiation binary targeted therapy for HER-2 positive breast cancers on: the effective drug delivery mechanism, the numerical model to evaluate the targeted radiation delivery and the survey study to find the neutron facility in the world that might be capable of producing the radiation effect as needed. A novel method of drug delivery utilizing Trastuzumab is described, followed by the description of a computational Monte Carlo based breast model used to determine radiation dose distributions. The total flux and neutron energy spectra of five currently available neutron irradiation treatment facilities are examined for this application. The tumour boron concentrations and tumour to healthy tissue concentration ratios required to deliver 50 Gy-Eq to the tumour without exceeding 18 Gy-Eq in the skin are determined, as well as the associated therapeutic ratios. Discussion is provided to address the future research direction for assessing the feasibility of the proposed concept.
Issue 6 (21 March 2006)
Received 18 October 2005, in final form 5 January 2006
Published 21 February 2006
Daniel W Mundy et al 2006 Phys. Med. Biol. 51 1377
Absar Ahmad et al 2003 Nanotechnology 14 824
P Defraigne and G Petit 2003 Metrologia 40 184
Z Dehouche et al 2005 Nanotechnology 16 402
P. J. Hoogerbrugge and J. M. V. A. Koelman 1992 Europhys. Lett. 19 155
Walter Bich et al 2006 Metrologia 43 S161
S Djordjevic et al 2008 Metrologia 45 429
Hans R Griem et al 2005 J. Phys. B: At. Mol. Opt. Phys. 38 975
Sun K Yoo et al 2002 Physiol. Meas. 23 469
H R Dullin et al 2000 Nonlinearity 13 203