Novel approach in radionuclide tumor therapy: Dose enhancement by high Z-element contrast agents

Purpose: The aim of this study was to first calculate the dose-enhancement effect from internalized radiation by the presence of exogenous contrast media using Monte Carlo simulations, and then provide in vitro proof-of-concept for this novel method of radiation-dose enhancement. Materials and Methods: The Monte Carlo program EGSnrc (Electron Gamma Shower) was used to simulate the interaction of internalizing radiation with iodine (I) or gadolinium (Gd) containing contrast media. Experimentally, the dose-enhancement effect induced by I or Gd was evaluated in cell culture assays using internalizing peptides chelated with beta(-) emitting radionuclides and clinically available contrast media. Results: Monte Carlo simulations predicted significant enhancement (similar to 70-340%) of radiation dose in the presence of high Z-element contrast media. This enhancement is radiation and Z-element dependent. Calculations showed that in the presence of contrast media, low-energy radionuclides favor localization of secondary particles, whereas higher energy beta(-) emitters localize radiation by reducing the pathway of the primary beta(-) particle. The dose enhancement was verified in vitro in two cell lines. Conclusions: Monte Carlo simulations in parallel with in vitro studies provide proof-of-principle for dose enhancement that occurs when utilizing an internalized source of radiation followed by the addition of exogenous contrast media. This dose enhancement is both radiation and Z-element dependent.