Development of an experimentally derived microscale blood and lymphatic vasculature model for applications to radiopharmaceutical dosimetry

In radiopharmaceutical therapy (RPT) applications, the use of alpha-emitting radionuclides is growing in popularity for treatment of cancer due to their high energy deposition and potential for localized targeting. The design of intravenously administered therapies leveraging the short-range of alpha particles (50-100 µm) requires accurate dosimetry calculations. Current computational models used for these calculations, however, do not include tissue level details that incorporate the spatial patterns associated with blood microvessels, lymphatic vessels, or other anatomically relevant details. The objective of this study was to develop a 3D computational, tissue mimic model incorporating physiologically relevant microvascular network patterns for calculating local alpha particle dosimetry effects. It is hypothesized that to compute scale-accurate alpha particle doses, explicitly modeled blood and lymphatic microvasculature must be considered in radiation transport simulations. To obtain relevant microvascular network patterns, adult rat mesenteric tissues labeled for PECAM (blood vessel marker) and Lyve-1 (lymphatic marker) were imaged. Representative images of network regions were then imported into the Creo Parametric software and converted to a 3D surface polygon mesh model that incorporated vessel diameters, lengths and patterns. Post conversion of the structures into a tetrahedral mesh with delineated material properties was performed using POLY2TET. The model was then incorporated into the Particle and Heavy Ion Transport code System (PHITS), a Monte Carlo-based radiation transport code, and absorbed fractions were computed for the blood microvessel, lymphatic and interstitial regions. Simulations were performed for alpha particles of energies 0.5-12 MeV in increments of 0.5 MeV. The applicability of our model framework was supported by the computation of absorbed doses for alpha particles. In the low energy simulations closer to 0.5 MeV, absorbed fractions in non-source target regions were approximately zero due to minimal escape from the source regions. Absorbed fractions approached the volume fraction of the target region with increasing energy source particle. Our results provide the first estimates of alpha particle absorbed doses associated with experimentally derived blood and lymphatic microvascular structures and serve to guide whether such tissue level detail should be considered in pre-clinical treatment planning.

Funding Provided by NCI Grant R01 CA248901

This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.