  Purpose: The introduction of Gold NanoParticles (GNPs) in radiotherapy
requires consideration of GNP size, location, and quantity, and more, as well
as beam quality. The work is presented in two parts, with Part I (this work)
investigating accurate and efficient MC modeling to calculate nucleus and
cytoplasm Dose Enhancement Factors (n,cDEFs). Part II then evaluates cell dose
enhancement factors across macroscopic length scales. Methods: Different
methods of modeling gold within cells are compared: a contiguous volume of
either pure gold or gold-tissue mixture or discrete GNPs. MC simulations with
EGSnrc are performed to calculate n,cDEF for a cell considering 10 to 370 keV
incident photons, gold concentrations from 4 to 24~mg of gold per gram, and
three different GNP configurations: GNPs distributed around the surface of the
nucleus or packed into one or four endosomes. Results: n,cDEFs are sensitive to
the model of gold in the cell, with differences of up to 17% observed between
models. Across cell/nucleus radii, source energies, and gold concentrations,
n,cDEF are highest for GNPs in the perinuclear configuration, compared with
GNPs in endosomes. Across all simulations of the default cell, nDEFs and cDEFs
range from one to 6.83 and 3.87, respectively. If the cell size is changed,
much higher n,cDEFs are observed. n,cDEF are maximized at photon energies at or
just above the K- or L-edges of gold. Conclusions: This work demonstrates many
physics trends on DEFs at the cellular level, including that cellular DEFs are
sensitive to gold modeling approach, GNP configuration, cell/nucleus size, gold
concentration, and incident source energy. These data will allow one to
optimize or estimate DEF using not only GNP uptake, but account for incident
photon energy and intracellular configuration of GNPs. Part II will expand the
investigation, applying the cell model in cm-scale phantoms.
