Dosimetric characterization of radionuclides for systemic tumor therapy: Influence of particle range, photon emission, and subcellular distribution

Abstract

Various radionuclides have been proposed for systemic tumor therapy. However, in most dosimetric analysis of proposed radionuclides the charged particles are taken into consideration while the potential photons are ignored. The photons will cause undesirable irradiation of normal tissue, and increase the probability of toxicity in, e.g., the bone marrow. The aim of this study was to investigate the dosimetric properties according to particle range, photon emission, and subcellular radionuclide distribution, of a selection of radionuclides used or proposed for radionuclide therapy, and to investigate the possibility of dividing radionuclides into groups according to their dosimetric properties. The absorbed dose rate to the tumors divided by the absorbed dose rate to the normal tissue (TND) was estimated for different tumor sizes in a mathematical model of the human body. The body was simulated as a 70-kg ellipsoid and the tumors as spheres of different sizes (1 ng-100 g). The radionuclides were either assumed to be uniformly distributed throughout the entire tumor and normal tissue, or located in the nucleus or the cytoplasm of the tumor cells and on the cell membrane of the normal cells. Fifty-nine radionuclides were studied together with monoenergetic electrons, positrons, and alpha particles. The tumor and normal tissue were assumed to be of water density. The activity concentration ratio between the tumor and normal tissue was assumed to be 25. The radionuclides emitting low-energy electrons combined with a low photon contribution, and the alpha emitters showed high TND values for most tumor sizes. Electrons with higher energy gave reduced TND values for small tumors, while a higher photon contribution reduced the TND values for large tumors. Radionuclides with high photon contributions showed low TND value for all tumor sizes studied. The radionuclides studied could be divided into four main groups according to their TND values: beta emitters, Auger electron emitters, photon emitters, and alpha emitters. The TND values of the beta emitters were not affected by the subcellular distribution of the radionuclide. The TND values of the Auger electron emitters were affected by the subcellular radionuclide distribution. The photon emitters showed low TND values that were only slightly affected by the subcellular radionuclide distribution. The alpha emitters showed high TND values that were only slightly affected by the subcellular radionuclide distribution. This dosimetric characterization of radionuclides may be valuable in choosing the appropriate radionuclides for specific therapeutic applications.

A model of cellular dosimetry for macroscopic tumors in radiopharmaceutical therapy

“…Traditionally, Monte Carlo models are made based on S-values decomposed into self-dose and cross-dose terms. 4,6,9,[11][12][13]42 However, as previously mentioned, the relatively low (10-1000) number of events per cell (N r ), typical of therapeutic regimens, would reduce the value of such average-value approaches in determining TCP since each individual cell's absorbed dose can significantly impact the dosimetric results and a substantial amount of fluctuation in the individual cell absorbed doses can be expected. Spaic et al …”

“…The TCP as an important dosimetric end point criterion, arguably the most important criterion, has been extensively discussed, 2,7,13,[37][38][39][40] mostly theoretically, including more recently by Bouchat et al 41 who introduce the concept of SCP or shell control probability as a radial dependent TCP. Traditionally, Monte Carlo models are made based on S-values decomposed into self-dose and cross-dose terms.…”

“…The traditional remedy consists of using point kernels obtained from Monte Carlo distributions, convoluted with activity distribution and using fast Fourier transforms to collect the energy in the volumes of interest. 1,9,13 However, this method relies on a statistically significant number of decays and a statistically significant ratio of number of decays to number of active cells in order that the radial distribution of the Monte Carlo-derived point kernel be reasonably valid isotropically and on an individual cell basis. Since the basis of comparison to experimental data is often TCP, which is most affected by the shape of the cell absorbed dose distribution rather than the average cell absorbed dose, especially by the outliers on the lower end of the distribution, 2,3 a method that does not take statistical averages is preferred.…”

A Proposed Methodology to Select Radioisotopes for Use in Radionuclide Therapy

“…There is, however, the potential to use these characteristics of manufactured radioisotopes to work in synergy rather than in detriment to the treatment goals. Uusijärvi et al 14 proposed dividing radionuclides into groups on the basis of their dosimetric properties, so that this characterization could be taken into account when choosing radionuclides for specific therapeutic applications. Specifically, the authors found differences in the dosage delivered to normal tissue among different types of emitters because of photon contribution in addition to the charged particles they emitted.…”

Radiochemical Separation of ¹⁶¹Tb from Gd/Tb Matrix Using Ln Resin Column

“…The dosimetric evaluation of therapeutic efficiency of electron emitting radiolanthanides shows that 161 Tb provides better energy transfer in small tumor than 177 Lu because of the high conversion and Auger electrons [12][13]. Accordingly, 161 Tb may be useful as a complement to 177 Lu due to its good tumor-to-normal-tissue mean absorbed dose ratios (TNDs) profile [11].…”