Prediction of normal tissue complication probability for rat spinal cord tolerance following ion irradiations.

Currently, treatment planning in cancer hadrontherapy relies on dose-volume criteria and physical quantities constraints. However, incorporating biologically related models of tumor control probability and of normal tissue complication probability (NTCP) would help further minimizing adverse tissue reactions, and would allow achieving a more patient-specific strategy. The aim of this work was therefore the development of a mechanistic approach to predict NTCP for late tissue reactions following ion irradiation.

The innovative Mn for positron emission tomography (PET) imaging: Production cross section modeling and dosimetric evaluation.

Background: Manganese is a paramagnetic element suitable for magnetic resonance imaging (MRI) of neuronal function. However, high concentrations of Mn can be neurotoxic. Mn may be a valid alternative as positron emission tomography (PET) imaging agent, to obtain information similar to that delivered by MRI but using trace levels of Mn , thus reducing its toxicity.

PREDICTING BIOLOGICAL EFFECTS ALONG HADRONTHERAPY DOSE PROFILES BY THE BIANCA BIOPHYSICAL MODEL.

The BIANCA biophysical model of cell death and chromosome aberrations was further refined and applied to predict the biological effectiveness along Spread-Out Bragg Peaks used in hadrontherapy. The simulation outcomes were compared with in vitro survival data on protons, He-ions and C-ions over a wide LET range, and the particle- and LET-dependence of the DNA Cluster Lesions (CLs) yields used as input parameters was investigated. For each particle type, the CL yield was found to increase with LET in a linear-quadratic fashion; fitting the CL yields allowed to predict cell death and chromosome aberrations in principle at any depth along a longitudinal proton dose profile used at CNAO.

BIANCA, a biophysical model of cell survival and chromosome damage by protons, C-ions and He-ions at energies and doses used in hadrontherapy.

An upgraded version of the BIANCA II biophysical model, which describes more realistically interphase chromosome organization and the link between chromosome aberrations and cell death, was applied to V79 and AG01522 cells exposed to protons, C-ions and He-ions over a wide LET interval (0.6-502 keV µm), as well as proton-irradiated U87 cells. The model assumes that (i) ionizing radiation induces DNA 'cluster lesions' (CLs), where by definition each CL produces two independent chromosome fragments; (ii) fragment (distance-dependent) mis-rejoining, or un-rejoining, produces chromosome aberrations; (iii) some aberrations lead to cell death.

Proximity effects in chromosome aberration induction: Dependence on radiation quality, cell type and dose.

It is widely accepted that, in chromosome-aberration induction, the (mis-)rejoining probability of two chromosome fragments depends on their initial distance, r. However, several aspects of these "proximity effects" need to be clarified, also considering that they can vary with radiation quality, cell type and dose. A previous work performed by the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model has suggested that, in human lymphocytes and fibroblasts exposed to low-LET radiation, an exponential function of the form exp(-r/r), which is consistent with free-end (confined) diffusion, describes proximity effects better than a Gaussian function.

Proximity effects in chromosome aberration induction by low-LET ionizing radiation.

Although chromosome aberrations are known to derive from distance-dependent mis-rejoining of chromosome fragments, evaluating whether a certain model describes such "proximity effects" better than another one is complicated by the fact that different approaches have often been tested under different conditions. Herein, a biophysical model ("BIANCA", i.e.

Calculating Variations in Biological Effectiveness for a 62 MeV Proton Beam.

A biophysical model of radiation-induced cell death and chromosome aberrations [called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA)] was further developed and applied to therapeutic protons. The model assumes a pivotal role of DNA cluster damage, which can lead to clonogenic cell death following three main steps: (i) a DNA "cluster lesion" (CL) produces two independent chromosome fragments; (ii) fragment mis-rejoining within a threshold distance d gives rise to chromosome aberrations; (iii) certain aberration types (dicentrics, rings, and large deletions) lead to clonogenic inactivation. The yield of CLs and the probability, f, that a chromosome fragment remains un-rejoined even if other fragment(s) are present within d, were adjustable parameters.