A physiology-based pharmacokinetic approach to calcitriol quantum dot distribution for use in inflammatory breast cancer treatment

Abstract

Inflammatory breast cancer (IBC) is a rare yet aggressive form of breast cancer accounting for 1-5% of breast cancer cases. Due to its typically delayed diagnosis and highly metastatic nature, IBC has the lowest overall survival rate compared to other forms of breast cancer. Current treatment uses an aggressive multi-targeting approach but is still not very successful. Recent studies have indicated that calcitriol, the active form of vitamin D, has beneficial effects again SUM149 IBC cell proliferation, migration, and differentiation. Calcitriol can be conjugated with quantum dots (QDs) to allow for live cell direct imaging. Furthermore, IBC targeting methods utilizing SM3 have been demonstrated as effective which provide a method to target calcitriol directly to tumors while also monitoring QD levels. Here, a top-down physiology-based pharmacokinetic model was constructed and demonstrated as a method to augment in vitro and in vivo testing to provide additional simulated information on the behavior of QD treatment strategies for use in IBC. Overall, we were able to construct an effective model to describe the system in question and found results consistent with experimental studies of similar systems. Further in vitro studies would allow for replacement of some currently estimated parameters with biologically relevant ones.

Margot Wagner

Postdoctoral Researcher

Interested in the use of data science and AI in mental health and using neuroscience to inspire next generation AI tools.