Mathematical modeling of phototoxicity during fluorescent imaging of tumor spheroids

Fluorescent live cell imaging is a widely used method in studying in vitro cell cultures, thus the behavior of in vitro tumor spheroids can be examined cheaply and simply over several days. However, during several days lasting experiments with many measurement points, the strong laser light that excites the fluorescent sample can have a destructive effect on living cells. This phenomenon is phototoxicity, the consideration of which is of fundamental importance during such long-term cytotoxicity measurements, in order to filter out those cell-damaging effects that did not occur as a result of the investigated chemotherapy agent. Modeling phototoxicity was the focus of this paper. Here we present two models of tumor dynamics tailored for in vitro tumor spheroids, containing tumor proliferation, tumor inhibition by chemotherapeutic agents, and inhibition by phototoxicity. The two models differ in the phototoxic term. Thus one of them describes phototoxicity as a continuous event during the measurement, while the other one approach this phenomenon as an impulsive effect. The model fitting and parameter estimation were carried out using the same cytotoxicity measurement data of tumor spheroids in both cases. We compared the fitting results of the two models by determining their worst case SSE values.