Calculated DNA damage from gadolinium Auger electrons and relation to dose distributions in a head phantom.
OBJECTIVE
To calculate the number of 157Gadolinium (157Gd) neutron capture induced DNA double strand breaks (DSB) in tumor cells resulting from epithermal neutron irradiation of a human head when the peak tissue dose is 10 Gy. To assess the lethality of these Gd induced DSB. MATRIALS AND METHODS: DNA single and double strand breaks from Auger electrons emitted during 157Gd(n,gamma) events were calculated using an atomistic model of B-DNA with higher-order structure. When combined with gadolinium neutron capture reaction rates and neutron and photon physical dose rates calculated from the radiation transport through a model of the human head with explicit tumors, peak tissue dose can be related to the number of Auger electron induced DSB in tumor cell DNA. The lethality of these DNA DSB were assessed through a comparison with incorporated 125I decay cell survival curves and second comparison with the number of DSB resulting from neutron and photon interactions.


RESULTS
These calculations on a molecular scale (microscopic calculations) indicate that for incorporated 157Gd, each neutron capture reaction results in an average of 1.56 +/- 0.16 DNA single strand breaks (SSB) and 0.21 +/- 0.04 DBS in the immediate vicinity (approximately 40 nm) of the neutron capture. In an example case of Gd Neutron Capture Therapy (GdNCT), a 1 cm radius midline tumor, peak normal tissue dose of 10 Gy, and a tumor concentration of 1000 ppm Gd, result in a maximum of 140 +/- 27 DSBs per tumor cell.


CONCLUSIONS
The number of DSB from the background radiation components is one order of magnitude lower than the Gd Auger electron induced DSB. The cell survival of mammalian cell lines with a similar amount of complex DSB induced from incorporated 125I decay yield one to two magnitudes of cell killing. These two points indicate that gadolinium auger electrons could significantly contribute to cell killing in GdNCT.
Goorley
Tim
T
Applied Physics, Los Alamos National Laboratory, X-Division, Mail Stop F663, Los Alamos, NM 87545, USA. jgoorley@lanl.gov
Zamenhof
Robert
R
Nikjoo
Hooshang
H
D001932:Brain Neoplasms; D002470:Cell Survival / Q000528:radiation effects; D003198:Computer Simulation; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004583:Electrons / Q000627:therapeutic use*; D005682:Gadolinium / Q000627:therapeutic use*; D006257:Head / Q000528:radiation effects; D007554:Isotopes / Q000627:therapeutic use; D008954:Models, Biological; D017247:Neutron Capture Therapy / Q000379:methods*; D011829:Radiation Dosage; D012062:Relative Biological Effectiveness; D016896:Treatment Outcome
D004273:DNA, Neoplasm; D007554:Isotopes; D005682:Gadolinium