Benchmark of a biophysical model for the radiobiology of RNT with 125I-labelled agents

The ISOLPHARM project, headed by INFN–LNL, is aimed at the production of exotic radionuclides of medical interest employing the Isotope Separation On-Line (ISOL) technique to develop innovative radiopharmaceuticals. In the last few years, the project has been focusing on the β-emitter silver-111 as a possible theranostic candidate for RadioNuclide Therapy (RNT). In this scenario, the therapeutic efficacy of radiolabelled compounds on cancer cells can be assessed by radiobiological trials, with the evaluation of the surviving fraction. The radiobiology of RNT is quite different from the one developed using external radiation beams, since it is characterised by lower dose rate, longer exposure and dependence on receptor–ligand kinetics. A biophysical model taking into account all these factors has been recently proposed by the ISOLPHARM collaboration and efforts are now being made to benchmark it with existing data. The key concept of the model is the subdivision of the cell culture in compartments with a progressive number of complex DNA lesions, while its purpose is to predict the time evolution of the irradiated cell population and, contextually, obtain a precise estimate of the dose rate per cell. The comparison of the predictions of the model with a reference study on Auger therapy using iodine-125 shows that a good agreement can be reached in almost all conditions studied under the assumption that the entire system dynamics is regulated by severe DNA lesions with 1% misrepair probability. The benchmark procedure also takes advantage of the Geant4-DNA Monte Carlo toolkit for the assessment of the model parameters identifying these lesions.