Estimation of absorbed radiation doses to skin and S-values for organs at risk due to nasal administration of PET agents using Monte Carlo simulations.

PURPOSE: The intranasal (IN) administration of radiopharmaceuticals is of interest in being a viable route for the delivery of radiopharmaceuticals that do not ordinarily cross the blood-brain barrier (BBB). However, to be viable in a patient population, good image quality as well as safety of the administration should be demonstrated. This work provides radiation dosimetry calculations and simulations related to the radiation safety of performing such experiments in a human cohort. METHODS: We performed Monte Carlo (MC) simulations to estimate radiation dose to the skin inside a cylindrical model of the nasal cavity assuming a homogenous distribution layer of 11 C and 18 F and calculated a geometry conversion factor (FP-C ) which can be used to convert from a planar geometry to a cylindrical geometry using more widely available software tools. We compared radiation doses from our simulated cylindrical geometry with the planar dose estimates employing our geometry conversion factor from VARSKIN 6.1 software and also from an analytical equation. Furthermore, in order to estimate radiation dosimetry to surrounding organs of interest, we performed a voxelized MC simulation of a fixed radioactivity inside the nasal cavity and calculated S-values to organs such as the eyes, thyroid, and brain. RESULTS: MC simulations of contamination scenarios using planar absorbed doses of 15.50 and 8.60 mGy/MBq for 18 F and 11 C, respectively, and 35.70 and 19.80 mGy/MBq per hour for cylindrical geometries, leading to determination of an FP-C of 2.3. Planar absorbed doses (also in units of mGy/MBq) determined by the analytical equation were 16.96 and 8.68 (18 F and 11 C) and using VARSKIN were 16.60 and 9.26 (18 F and 11 C), respectively. Application of FP-C to these results demonstrates values with a maximum difference of 9.41% from the cylindrical geometry MC calculation, demonstrating that when accounting for geometry, more simplistic techniques can be utilized to estimate IN dosimetry. Voxelized MC simulations of radiation dosimetry from a fixed source of 1 MBq of activity confined to the nasal cavity resulted in S-values to the thyroid, eyes, and brain of 1.72 x 10-6 , 1.93 x 10-5 , and 3.51 x 10-6  mGy/MBq·s, respectively, for 18 F and 1.80 × 10-6 , 1.95 × 10-5 , and 3.54 × 10-6  mGy/MBq·s for 11 C. CONCLUSION: Dosimetry concerns about IN administrations of PET radiotracers should be considered before clinical use. Values presented in the simulations such as the S-values can be further used for assessment of absorbed doses in cases of IN administration, and can be used to develop and adapt specific study protocols. All three presented methods provided similar results when considering the use of a geometry conversion factor for planar to cylindrical geometry, demonstrating that standard tools rather than dedicate MC simulations may be used to perform dose calculations in nasal administrations.

Maintenance of Near Normal Bone Mass and Architecture in Lethally Irradiated Female Mice following Adoptive Transfer with as few as 750 Purified Hematopoietic Stem Cells.

Total-body irradiation (TBI) followed by transfer of bone marrow cells from donors is routinely performed in immunology research and can be used to manipulate differentiation and/or function of bone cells. However, exposure to high-dose radiation can result in irreversible osteopenia, and transfer of heterogeneous cell populations can complicate interpretation of results. The goal of this research was to establish an approach for reconstituting bone marrow using small numbers of purified donor-derived hematopoietic stem cells (HSCs) without negatively affecting bone metabolism. Gamma-irradiated (9 Gy) WBB6F1 mice were engrafted with bone marrow cells (5 × 106 cells) or purified HSCs (3,000 cells) obtained from GFP transgenic mice. In vivo analysis and in vitro differentiation assays performed two months later established that both methods were effective in reconstituting the hematopoietic compartment with donor-derived cells. We confirmed these findings by engrafting C57Bl/6 (B6) mice with bone marrow cells or purified HSCs from CD45.1 B6 congenic mice. We next performed adoptive transfer of purified HSCs (750 cells) into WBB6F1 and radiosensitive KitW/W-v mice and evaluated the skeleton two months later. Minimal differences were observed between controls and WBB6F1-engrafted mice that received fractionated doses of 2 × 5 Gy. Kitw/wv mice lost weight and became osteopenic after 2 × 5 Gy irradiations but these abnormalities were negligible after 5 Gy irradiation. Importantly, adoptive transfer of wild-type cells into Kitw/wv mice restored normal Kit expression in bone marrow. Together, these findings provide strong evidence for efficient engraftment with purified HSCs after lethal TBI with minimal collateral damage to bone. This approach will be useful for investigating mechanisms by which hematopoietic lineage cells regulate bone metabolism.

SCALING PARAMETERS FOR HOT-PARTICLE BETA DOSIMETRY.

Scaling of dose-point kernel (DPK) values for beta particles transmitted by high-Z sources will overestimate dose at shallow depths while underestimating dose at greater depths due to spectral hardening. A new model has been developed based on a determination of the amount of monoenergetic electron absorption that occurs in a given source thickness through the use of EGSnrc (Electron Gamma Shower) Monte Carlo simulations. Integration over a particular beta spectrum provides the beta-particle DPK following self-absorption as a function of source thickness and radial depth in water, thereby accounting for spectral hardening that may occur in higher-Z materials. Beta spectra of varying spectral shapes and endpoint energies were used to test the model for select source materials with 7.42 ≤ Z ≤ 94. The results demonstrate that significant improvements can be made to DPK-based dosimetry models when dealing with high-Z volumetric sources. This new scaling model is currently being used to improve the accuracy of the beta-dosimetry calculations in VARSKIN 5.