Dosimetric evaluation and beam characterization of pair production enhanced radiotherapy (PPER) with the use of organometallics.

The current study evaluates dosimetric and spectral effects when platinum (Pt)-based chemotherapeutics and less toxic tungstophosphoric-acid (TPA) organometallics are present during x-ray radiotherapy. We hypothesize that the use of high energy photon beams (i.e. 18 MV) will increase absorbed dose due to increased pair production from high Z elements and thus result in additional tumor cell kill. EGSnrc code was used to examine the contribution of pair production to dose in the presence of the high Z material (TPA, Pt mixtures and tungsten, W) as a function of beam energy. Variables included different concentrations (100μmolar, 1mmolar), depths (5mm, 10cm), thicknesses (5mm, 5cm) and energies (6, 18MV). Overall, for the deeper depth, the 511keV photon fluence increase was up 31% (18MV-1mmolar) while at 6MV it was between 10-11% depending on the concentration. For the shallower depth, 18MV fluence increase was up 14.6% (1mmolar) and 18.6% (1mmolar) for the 6MV. The dose enhancement effect due to pair production was up 25-30% and a total 33-58% depending on the depth. The benefit related to pair production was more for 18MV and under conditions that simulated a realistic clinical setup. While part of the effect could be attributed to photoabsorption, a significant contribution of dose could result from pair production. Experimental clonogenic survival assay was consistent with the theory in that the low dose shoulder region of a cell survival curve was reduced using TPA and 18 MV compared with TPA and 6 MV or compared with no TPA and 18 MV; RBE was approximately 2 at the dose commonly used in conventional fractionated clinical radiotherapy. This suggests a potential new strategy for dose enhancement based on pair production using higher energy beamlines.