Introduction: 18F-FDG Positron emission tomography/computed tomography (PET/CT) is limited in evaluating prostate cancer (PCa) due to low glycolysis in the primary tumor. Recently, PET/CT targeting the prostate specific membrane antigen (PSMA) has been useful for the diagnosis of biochemical recurrence and subsequent radioligand therapy (RLT). So far, there are limited reports on the value of PSMA PET/CT in detecting primary tumors of the prostate gland. We conducted this study to evaluate the values of 18F-PSMA-1007 and 18F-FDG PET/CT in the primary tumor detection and understand metabolic heterogeneity and related clinicopathologic characteristics at initial presentation. Methods: This prospective study included 73 tumor regions from 42 patients who underwent both 18F-PSMA-1007 and 18F -FDG PET/CT and subsequent radical prostatectomy. SUVmax of the primary tumors on 18F-PSMA-1007 PET/CT were compared with the histological subtype and Gleason score (GS) by Kruskal-Wallis test with Bonferroni correction and with tumor size, serum PSA, and pathological stage (pStage). GS 6 and 7 were considered low and 8 to 10 were high. pStage I and II were considered early and the rest was advanced. Immunohistochemistry (IHC) was done for glucose transporter, PSMA, and androgen receptor (AR) expression. Results: 18F-PSMA-1007 PET/CT detected all primary tumors with a detection sensitivity of 100% (73/73) whereas 18F-FDG PET/CT detected only 16% (12/73). When tumors were classified into low-GS acinar, high-GS acinar, and high-GS ductal types, SUVmax of 18F-PSMA-1007 uptake was significantly different among the three groups (SUVmax 8.9 in low-GS acinar, 14.7 in high-GS ductal, and 33.9 in high-GS acinar, all p values < 0.05). In addition, high 18F-PSMA-1007 uptake was correlated with high serum PSA level, and advanced pStage. There were 12 primary lesions with both 18F-PSMA and 18F-FDG uptake demonstrating a flip-flop phenomenon between the two radiotracer uptake; the foci of increased 18F-FDG uptake showed low 18F-PSMA-1007 uptake and vice versa. All were advanced in pStage with low AR expression on IHC and most of them (9/12) were large ductal tumors. Conclusions: 18F-PSMA-1007 PET/CT was excellent in detecting primary tumors of all GS in the prostate gland. Some primary tumors showed a reciprocal pattern of 18F-PSMA-1007 and 18F-FDG uptake which were mostly large ductal type with low AR expression. Further studies are needed to see whether tumors with 18F-FDG uptake may predict treatment resistance to androgen deprivation therapy and PSMA RLT. SOURCE OF Funding: None.