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 (100 µmolar, 1 mmolar), depths (5 mm, 10 cm), thicknesses (5 mm, 5 cm) and energies (6, 18 MV). Overall, for the deeper depth, the 511 keV photon fluence increase was up 31% (18 MV-1 mmolar) while at 6 MV it was between 10%-11% depending on the concentration. For the shallower depth, 18 MV fluence increase was up 14.6% (1 mmolar) and 18.6% (1 mmolar) for the 6 MV. 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 18 MV 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.