Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture Therapy.

Accurate dosimetry and determination of the biological effectiveness of boron neutron capture therapy (BNCT) is challenging because of the mix of different types and energies of radiation at the cellular and subcellular levels. In this paper, we present a computational, multiscale system of models to better assess the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) of several neutron sources as applied to BNCT using boronophenylalanine (BPA) and a potential monoclonal antibody (mAb) that targets HER-2-positive cells with Trastuzumab. The multiscale model is tested against published in vitro and in vivo measurements of cell survival with and without boron.

Dosimetric characteristics of the University of Washington Clinical Neutron Therapy System.

The University of Washington (UW) Clinical Neutron Therapy System (CNTS), which generates high linear energy transfer fast neutrons through interactions of 50.5 MeV protons incident on a Be target, has depth-dose characteristics similar to 6 MV x-rays. In contrast to the fixed beam angles and primitive blocking used in early clinical trials of neutron therapy, the CNTS has a gantry with a full 360° of rotation, internal wedges, and a multi-leaf collimator (MLC).

DNA double strand break (DSB) induction and cell survival in iodine-enhanced computed tomography (CT).

A multi-scale Monte Carlo model is proposed to assess the dosimetric and biological impact of iodine-based contrast agents commonly used in computed tomography. As presented, the model integrates the general purpose MCNP6 code system for larger-scale radiation transport and dose assessment with the Monte Carlo damage simulation to determine the sub-cellular characteristics and spatial distribution of initial DNA damage. The repair-misrepair-fixation model is then used to relate DNA double strand break (DSB) induction to reproductive cell death.

MCNP6 model of the University of Washington clinical neutron therapy system (CNTS).

A MCNP6 dosimetry model is presented for the Clinical Neutron Therapy System (CNTS) at the University of Washington. In the CNTS, fast neutrons are generated by a 50.5 MeV proton beam incident on a 10.

Rapid MCNP simulation of DNA double strand break (DSB) relative biological effectiveness (RBE) for photons, neutrons, and light ions.

To account for particle interactions in the extracellular (physical) environment, information from the cell-level Monte Carlo damage simulation (MCDS) for DNA double strand break (DSB) induction has been integrated into the general purpose Monte Carlo N-particle (MCNP) radiation transport code system. The effort to integrate these models is motivated by the need for a computationally efficient model to accurately predict particle relative biological effectiveness (RBE) in cell cultures and in vivo. To illustrate the approach and highlight the impact of the larger scale physical environment (e.

Hepatic structural dosimetry in (90)Y microsphere treatment: a Monte Carlo modeling approach based on lobular microanatomy.

Unlabelled: Selective internal radiation treatment (SIRT) via intrahepatic arterial administration of (90)Y microspheres is an effective therapeutic modality. The conventional and generally applied MIRD schema is based on the premise that the distribution of microspheres in the liver parenchyma is uniform. In reality, however, the distribution of the microspheres follows a distinct pattern, requiring that a model be developed to more appropriately estimate radiation absorbed doses to the different structural/functional elements of the hepatic microanatomy.

Numerical assessment of radiation binary targeted therapy for HER-2 positive breast cancers: advanced calculations and radiation dosimetry.

In our previous publication (Mundy et al 2006 Phys. Med. Biol.

Radiation binary targeted therapy for HER-2 positive breast cancers: assumptions, theoretical assessment and future directions.

A 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.

MCNP5 evaluation of dose dissipation in tissue-like media exposed to low-energy monoenergetic X-ray microbeam.

Following a significant increase in the number of facilities in the world having and developing low- and high-linear energy transfer (LET) microbeams for experimental radiobiological studies, it is useful and demanding to establish reliable computational models to analyze such experiments. This paper summarizes initial MCNP5 calculations of the basic parameters needed to study X-ray microbeam penetration, dose deposition and dose spatial dissipation in tissue-like media of micro and macro scales. The presented models can be used to predict doses delivered to neighboring cells and analyze the cause of bystander cell deaths.

Computational assessment of improved cell-kill by gadolinium-supplemented boron neutron capture therapy.

Potential improvement in neutron capture therapy (NCT) by utilizing both 157Gd and 10B is assessed considering two parameters calculated in transport models in MCNP4B, the dose to quiescent cells and the therapeutic ratio. Improved sterilization of quiescent or more generally non-uptaking cells is demonstrated with the addition of 157Gd to conventional 10B loading. The improved dose delivery to non-uptaking cells from concurrent administration of 157Gd and 10B is weighed against a second index, degradation in the therapeutic ratio resulting from the longer interaction lengths of the 157Gd capture products.