Tumour targeting with stable and radioactive nuclides : Dosimetric aspects at the cellular level

Abstract: Targeting with radioactive nuclides or nuclides that can be activated by neutrons may be a powerful tool for treatment of invasive tumours and disseminated tumour cells. The targeting agents are designed to find tumour cells and deliver the nuclides. The aim of the thesis was to investigate the dosimetry at the cellular level for three forms of radiation of interest for targeted radiotherapy: neutron activated emission of 4He- and 7Li- ions from 10B; high energy β-particles from 131I and α- particles from 211At. Computer models of cells and groups of cellswere developed for Monte Carlo simulations and point dose kernel calculations of the energy depositions in the cell nuclei.Simulations of boron neutron capture therapy (BNCT), mostly with a thermal neutron fluence of 5x1012 cm-2, showed that 108 atoms of 10B per cell always gave too low doses. Located in the nucleus, 109 atoms of 10B gave therapeutically interesting doses while location elsewhere in the cell gave insufficient dose to the nucleus. Boron dependent enhancement of tumour doses in fast neutron therapy demand at least 100 ppm of 10B in the tumour cells, a concentration at which BNCT, compared to fast neutron therapy, showed to give higher tumour doses and lower doses to normal tissue.With 105 atoms of 131I per cell and an effective half-life of 24 h the 131I had to be located in the nucleus to give therapeutically interesting doses in single cells. However, in tumour cell clusters with a diameter larger than 40 µm therapeutic doses were reached due to crossfire irradiation.211At is a most promising radionuclide for targeting of single cells or microscopic metastases. Between 30 and 1000 atoms of 211At per cell, depending on cell size and position of 211At, suffice to deliver, on the average, 10 Gy in the nucleus of a single cell, a dose relevant for therapy.