125I brachytherapy k-edge dose enhancement with AgTPPS4

Photon activation is a radiotherapy technique in which an element is added to the absorbing medium to raise the probability that a photoelectric interaction will occur, thus causing an increase in the absorption of ionizing radiation. Binding energies of key elements within an absorbing medium are closely matched with the incident photon energies to maximize the production of free electrons and subsequent absorption of their kinetic energies. The purpose of this research was to quantify potential dose enhancement using a silver tetraphenyl sulfonato porphyrin (AgTPPS4) in tumors as a photon activator for use with interstitial 125I brachytherapy. A three-dimensional Monte Carlo dosimetry model was developed using the EGS4 coding system. The photon source was modeled using spectral gamma emissions from models 6702 or 6711 brachytherapy seeds for comparison. Absorbed dose within the tumor volume was calculated for AgTPPS4 concentrations ranging between 0 and 20 mmol/kg tumor weight. These theoretical studies demonstrated linear increases in dose absorbed by the tumor with corresponding increases in AgTPPS4 concentration. The required AgTPPS4 concentration (RSC) to achieve at least a ten percent absorbed dose increase is approximately 6.5 mmol/kg tumor weight for model 6702 seeds. In vivo biodistribution and in vitro toxicity studies were conducted to determine if the theoretically derived RSC could be achieved biologically. Cell toxicity studies showed that TPPS4 porphyrin derivatives were cytotoxic at concentrations required to provide significant brachytherapy dose enhancement. Reverse phase HPLC confirmed that toxicity was due to intrinsic properties of the TPPS4 molecule, not the presence of free silver, drug impurities, or metabolites. Further research is necessary to develop a nontoxic molecular carrier for delivering silver to the DNA of tumor cells.