Experimentally Derived Microscale Blood and Lymphatic Vasculature Models for Applications to Radiopharmaceutical...

The objective of this study was to develop 3D computational, tissue mimic models incorporating physiologically relevant microvascular network patterns for computing local alpha-particle dosimetry and to explore the impact of network variability.

To obtain relevant microvascular network patterns, adult rat mesenteric tissues labeled for PECAM and Lyve-1 were imaged. Images were used to create 3D polygon mesh models which were then tetrahedralized with delineated material properties. The models were subsequently incorporated into a Monte Carlo-based radiation transport code and absorbed fractions-defined as the fraction of particle energy emitted from a source region that is deposited within a target region-were computed for the blood microvessels, lymphatic microvessels, and interstitial parenchyma tissue regions.

A data set of absorbed fractions for alpha particles and electrons in each of the regions in the eight generated models acting as sources and targets was generated, noting the differences from previously used models that rely on a homogenization of both tissue and blood. Absorbed fractions approached the volume fraction of the target region with increasing energy source particle as expected. Variations in absorbed fractions up to 30% were observed between models.

Our results provide the first estimates of alpha particle and electron absorbed fractions associated with experimentally derived blood and lymphatic microvascular structures. The work suggests the importance of considering microvascular density, vessel diameters, and spatial location for tissue dosimetry in radiopharmaceutical therapy.