Dosimetry and Microdosimetry of Targeted Radiotherapy

Abstract

Dosimetry in targeted radiotherapy (TR) uses different calculation methods, whose degree of refinement is closely conditioned by the particular objective sought. It is more generally performed to establish a correlation between the quantity of radiation delivered to a target and the biological damage observed or that can be reliably predicted. It can thus be used to optimise treatments and allow comparison of different therapeutic approaches, as well as to study the basic methods of irradiation of biological matter. Two broad types of investigations can be found in the literature: microdosimetric ones (stochastic approaches used to study energy deposits) and macrodosimetric ones (non-stochastic or deterministic approaches). The mathematical formalism is consistent between these two types, and the calculation methods currently used are often similar. This review presents different approaches to the dosimetry of radionuclides used in TR. The introduction defines the general problem, the role of dosimetry in TR and the specific problems raised by targeting (non-uniformity of source distributions). The first part considers the types of calculation methods found in TR in relation to the basic quantities used to represent stochastic energy deposit on a cellular scale. In particular, it compares the formalism and the methods used in microdosimetric or conventional macrodosimetric approches. Although microdosimetry, or even track structure calculations, can provide the basic elements for modelling the absorbed dose process, a simplified dosimetric approach may be adequate to describe the phenomena observed. The scheme proposed by the MIRD committee relates to such an approach and is presented together with other methods allowing the calculation of the mean dose delivered (analytic methods, dose point kernels, Monte-Carlo, etc.). The second part shows the application range for the various methods, providing selected examples of dosimetric approaches in TR on different scales, from the organ (or tissues) to the cell or even DNA, and a brief presentation of bone marrow dosimetry.

Calculation of cellular S-values using Geant4-DNA: The effect of cell geometry

“…For instance, In-111 and I-125 emit, on average, $ 8 and $ 25 electrons per decay, respectively, with energies between (approximately) 12 eV and 24 keV (Kassis, 2003). Their short irradiation range ( $ nm to $μm), however, places higher demands on the sub-cellular distribution of the Auger-emitting radionuclides (Bardiès and Pihet, 2000). Thus, the high radiotoxicity of Auger emitters critically depends on the proximity of the decaying site to DNA (Kassis and Adelstein, 2005).…”

Quantitative imaging for clinical dosimetry

“…For example, it is possible to subdivide a target region into smaller target regions if the relative standard deviation associated with the mean absorbed dose becomes too high, in order to define a volume in which the delivered absorbed dose does not deviate too much from the mean. This implies that statistical fluctuations cannot be considered in this formalism, although spatial variability can [4].…”

Review of Geant4-DNA applications for micro and nanoscale simulations

“…For example, in Targeted Particle (alpha, beta, Auger) Therapy, the calculation of energy deposition at cellular level is necessary because of the short path length of particles emitted by the radionuclide and the spatial distribution of the radionuclide relative to the small target volumes [16,17]. The investigation of high-Z nanoparticles (NP) as radiosensitisers has demonstrated the need to investigate the effect of radiation at nanoscale [18].…”