Disclosed herein are methods for determining suitability of biology-guided radiotherapy (BgRT). These methods may include converting diagnostic positron emission tomography (PET) imaging data to simulated imaging data consistent with images obtained using PET detectors of a BgRT radiotherapy system. The simulated imaging data may be used to evaluate the suitability of BgRT by evaluating a first metric indicating a contrast noise ratio for a tumor, a second metric indicating a PET tracer activity concentration, and a third metric indicating a radiation dose to the tumor. Also disclosed herein are methods for generating synthetic or simulated list mode LOR data from one or more PET images. The synthetic or simulated list mode data may be used for testing BgRT algorithms and/or determining whether BgRT is suitable for a patient.