PurposeTo compare the block sequential regularized expectation maximization (BSREM) algorithm with the ordered subsets expectation maximization (OSEM) algorithm and to evaluate how different penalty factors (bvalues) influence image quality and SUV measurements.MethodsWe analyzed data from 78 prostate cancer patients who underwent68Ga-RM2 (n = 42) or68Ga-prostate-specific membrane antigen (PSMA)-11 (n = 36) PET/MRI. The raw PET data were retrospectively reconstructed using both time-of-flight (TOF)–BSREM withbvalues of 250, 350, 500, 750, and 1000 and TOF-OSEM. Each reconstruction was reviewed independently by 3 nuclear medicine physicians and scored qualitatively using a Likert scale (1 = poor, 5 = excellent quality). SUV measurements were analyzed as well.ResultsFifty-seven lesions were detected (21 on68Ga-RM2 and 36 on68Ga-PSMA-11 PET/MRI); SUVmax decreased with the increase of β values for both tracers. Background noise (SUVsd) decreased with increasing of β values for both tracers. The mean ± SD scores for68Ga-RM2 PET images were 2.4 ± 0.5 forb= 250 reconstructions, 3.2 ± 0.6 forb= 350, 4 ± 0.6 forb= 500, 4.5 ± 0.5 forb= 750, 4.4 ± 0.7 forb= 1000, and 3.4 ± 0.6 for TOF-OSEM. The mean ± SD scores for68Ga-PSMA-11 PET images were 3.2 ± 0.8 forb= 250 reconstructions, 4.1 ± 0.8 forb= 350, 4.7 ± 0.6 forb= 500, 4.8 ± 0.4 forb= 750, 4.7 ± 0.6 forb= 1000, and 3.8 ± 0.5 for TOF-OSEM.ConclusionsTime-of-flight–BSREM algorithm improves image quality. Differentbvalues should be used for different68Ga-labeled radiopharmaceuticals such as those targeting GRPR and PSMA receptors. Once selected, the samebvalue should be consistently used because SUVmax measurements differ with differentbvalues.