Clinical significance of atomic inner shell ionization (ISI) and Auger cascade for radiosensitization using IUdR, BUdR, platinum salts, or gadolinium porphyrin compounds.
OBJECTIVE
Halogenated pyrimidines (iododeoxyuridine [IUdR] and bromodeoxyuridine [BUdR]), platinum salts, and gadolinium porphyrins are heavy atom compounds used as radiosensitizers. For IUdR, it has been hypothesized that iodine inner shell ionizations (ISI) and Auger cascades could be one of the primary radiosensitization mechanisms. The purpose of this paper is to estimate the number of ISI produced per tumor cell and per 2 Gy irradiation in clinically relevant modelings.


METHODS
ISI were evaluated using a two-step method. Photon-induced ISI were calculated using the MCNP-4C Monte Carlo code, heavy atom concentrations from clinical data published in the literature, and at various depths in a water phantom irradiated with 6-MV, (60)Co, (137)Cs, or (192)Ir sources. Electron knock-on induced ISI on K, L, and M atomic shells were evaluated with an hybrid method, using simulated electron spectra and cross-sections derived from the Møller formalism. Using a biological dose equivalence of 0.05 Gy per cell ISI, relative biological effectiveness (RBE) values were calculated for each situation.


RESULTS
For platinum and gadolinium, ISI occurs in far less than 0.1% of the cell, whichever is the configuration. For IUdR and BUdR, ISI occurs in between 45% to 483% of the cell. Due to spectrum degradation, about 3 times more photoelectric ISI are generated at greater than shallower depths, and 10 times more for (192)Ir compared with (60)Co or 6-MV X-rays. Photoelectric ISI are about 3 times more frequent for iodine than bromine, but electron knock-on ISI are more frequent on bromine, and at the end about the same number of ISI are generated for both elements. RBEs were found to be between 1.01 and 1.12 for clinically relevant irradiation settings.


CONCLUSIONS
The mechanisms of radiosensitization for platinum and gadolinium are clearly not related to an Auger cascade. For halogenated pyrimidines, however, clinically relevant numbers of ISI are generated within each cell. For IUdR, ISI appears to be strongly tied to the photon spectra. Halogenated pyrimidines should be evaluated again clinically, but using lower energy photons like a (192)Ir implant.
Pignol
Jean-Philippe
JP
Department of Radiation Oncology, Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada. Jean-Philippe.Pignol@tsrcc.on.ca
Rakovitch
Eileen
E
Beachey
David
D
Le Sech
Claude
C
D001973:Bromodeoxyuridine / Q000737:chemistry* / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics; D007065:Idoxuridine / Q000737:chemistry* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D009010:Monte Carlo Method; D019047:Phantoms, Imaging; D010984:Platinum / Q000737:chemistry / Q000493:pharmacokinetics; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D012062:Relative Biological Effectiveness
D007457:Iodine Radioisotopes; D011838:Radiation-Sensitizing Agents; D010984:Platinum; D005682:Gadolinium; D001973:Bromodeoxyuridine; D007065:Idoxuridine