Using Cherenkov radiation in positron emission tomography (PET) has the potential to improve the time of flight (TOF) resolution and reduce the cost of detectors. In previous studies promising TOF results were achieved when lead fluoride (PbF2) crystals were used instead of a scintillator. In this work, a whole-body PbF2 Cherenkov TOF-PET scanner was simulated and optimized. Different configurations of the PbF2 crystals and their surface treatment were considered. Also evaluated was the influence of the crystal-photodetector coupling and of the detection efficiency of the photodetectors. Of special interest is a whole-body PbF2 Cherenkov TOF-PET scanner with a multi-layer detector, which improves the time resolution and reduces the parallax error, without compromising the detection efficiency. Images of a phantom were reconstructed for different configurations of the simulated whole-body PbF2 Cherenkov TOF-PET scanner and the quality of images was compared to that of a whole-body TOF-PET scanner with standard LSO scintillators. The TOF resolution of the whole-body PbF2 Cherenkov TOF-PET scanner with a multi-layer detector was 143 ps FWHM, out of which the fundamental limitation due to light production and transportation was only 22 ps FWHM.