AbstractWe aim to synthesize brain time‐of‐flight (TOF) PET images/sinograms from their corresponding non‐TOF information in the image space (IS) and sinogram space (SS) to increase the signal‐to‐noise ratio (SNR) and contrast of abnormalities, and decrease the bias in tracer uptake quantification. One hundred forty clinical brain 18F‐FDG PET/CT scans were collected to generate TOF and non‐TOF sinograms. The TOF sinograms were split into seven time bins (0, ±1, ±2, ±3). The predicted TOF sinogram was reconstructed and the performance of both models (IS and SS) compared with reference TOF and non‐TOF. Wide‐ranging quantitative and statistical analysis metrics, including structural similarity index metric (SSIM), root mean square error (RMSE), as well as 28 radiomic features for 83 brain regions were extracted to evaluate the performance of the CycleGAN model. SSIM and RMSE of 0.99 ± 0.03, 0.98 ± 0.02 and 0.12 ± 0.09, 0.16 ± 0.04 were achieved for the generated TOF‐PET images in IS and SS, respectively. They were 0.97 ± 0.03 and 0.22 ± 0.12, respectively, for non‐TOF‐PET images. The Bland & Altman analysis revealed that the lowest tracer uptake value bias (−0.02%) and minimum variance (95% CI: −0.17%, +0.21%) were achieved for TOF‐PET images generated in IS. For malignant lesions, the contrast in the test dataset was enhanced from 3.22 ± 2.51 for non‐TOF to 3.34 ± 0.41 and 3.65 ± 3.10 for TOF PET in SS and IS, respectively. The implemented CycleGAN is capable of generating TOF from non‐TOF PET images to achieve better image quality.