Mathematical Modeling of $^{18}$F-Fluoromisonidazole ($^{18}$F-FMISO) Radiopharmaceutical Transport in Vascularized Solid Tumors

TL;DR

This study develops a multi-scale mathematical model to analyze how tumor vascularization affects the transport and uptake of the radiopharmaceutical $^{18}$F-FMISO, providing insights into hypoxia imaging in solid tumors.

Contribution

It introduces a novel multi-scale spatiotemporal model that simulates radiopharmaceutical transport in tumors with different vascular architectures, incorporating complex physiological factors.

Findings

Higher microvascular density enhances radiopharmaceutical uptake.

Diffusion dominates over convection in transport mechanisms.

Transport dynamics vary with tumor growth stages.

Abstract

$^{18}$F-Fluoromisonidazole ($^{18}$F-FMISO) is a highly promising positron emission tomography radiopharmaceutical for identifying hypoxic regions in solid tumors. This research employs spatiotemporal multi-scale mathematical modeling to explore how different levels of angiogenesis influence the transport of radiopharmaceuticals within tumors. In this study, two tumor geometries with heterogeneous and uniform distributions of capillary networks were employed to incorporate varying degrees of microvascular density. The synthetic image of the heterogeneous and vascularized tumor was generated by simulating the angiogenesis process. The proposed multi-scale spatiotemporal model accounts for intricate physiological and biochemical factors within the tumor microenvironment, such as the transvascular transport of the radiopharmaceutical agent, its movement into the interstitial space by diffusion and convection mechanisms, and ultimately its uptake by tumor cells. Results showed that both quantitative and semi-quantitative metrics of $^{18}$F-FMISO uptake differ spatially and temporally at different stages during tumor growth. The presence of a high microvascular density in uniformly vascularized tumor increases cellular uptake, as it allows for more efficient release and rapid distribution of radiopharmaceutical molecules. This results in enhanced uptake compared to the heterogeneous vascularized tumor. In both heterogeneous and uniform distribution of microvessels in tumors, the diffusion transport mechanism has a more pronounced than convection. The findings of this study shed light on the transport phenomena behind $^{18}$F-FMISO radiopharmaceutical distribution and its delivery in the tumor microenvironment, aiding oncologists in their routine decision-making processes.