Intensity-modulated radiation therapy (IMRT) is a type of external beam radiation therapy used in cancer treatment. In IMRT, the prescribed radiation dose can be administered such that it is maximized on the cancerous tumor while sparing the surrounding healthy tissues. The total dose is divided into fractions across time intervals, called a fractionation scheme. To find the best fractionation scheme and beamlet intensities for total dose, optimization models are used. In this paper, a non-convex mixed-integer nonlinear programming model has been proposed wherein the spatiotemporal changes of the biological properties of the tumor due to tumor cell re-oxygenation, redistribution, and re-population that occur as the treatment progresses have been considered. Also, the dose constraints over both cumulative limits and per-fraction limits have been considered in the model. The output of this model is called the fractionation scheme and beamlet intensities considering biological changes in tumor cells (FBBTs). When the FBBTs are compared with conventional fractionation scheme and beamlet intensities (CFB) which do not include the biological properties of the tumor, it is observed that the FBBTs are more efficacious than the CFBs. To get FBBTs for datasets that resemble realistic tumors, an algorithm based on simulated annealing has been developed and used.