Head-to-head comparisons of ⁶⁸Ga-PSMA-11 and ¹⁸F-FDG PET/CT in evaluating patients with upper tract urothelial carcinoma: a prospective pilot study

PurposeTo prospectively compare the uptake of Ga-68-prostate specific membrane antigen (Ga-68-PSMA)-11 and F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) in upper tract urothelial carcinoma (UTUC) and investigate the correlation between radiological parameters and pathological features of UTUC.MethodsClinicopathologic and imaging data were collected from 10 UTUC patients who underwent preoperative Ga-68-PSMA-11 and F-18-FDG PET/CT scans. The diagnostic capabilities of both imaging techniques were analyzed and compared in UTUC. Angiogenesis in the malignancies was assessed using Chalkley counting and the expression of folate hydrolase 1 (FOLH1) and glucose transporter 1 (GLUT1) in UTUC were evaluated in the surgical specimens. Double immunofluorescence staining of PSMA and CD34 was used to examine tumor neovascularization. Tracer uptake and expression were compared and explored. Additionally, 10 patients with clear cell renal cell carcinoma (ccRCC) were included for prospective, comparative research.ResultsTen UTUC patients with 12 malignant lesions and another 10 ccRCC patients were included. F-18-FDG PET/CT demonstrated a more effective detection of UTUC foci compared to Ga-68-PSMA-11 PET/CT (the SUVmax of 18.48 & PLUSMN; 6.73 vs. 4.38 & PLUSMN; 1.45, P < 0.01). Immunohistochemical analysis revealed a statistically significant difference in the expression of PSMA and GLUT1 in UTUC (P = 0.048), with higher pathological grades showing more intense GLUT1 staining than PSMA (75% vs. 12.5%). The Chalkley counting of angiogenesis in ccRCC was significantly higher than that in UTUC (229.34 vs. 71.67), which was proportional to Ga-68-PSMA-11 PET/CT SUVmax (both P < 0.05).Conclusion(18)F-FDG PET/CT holds better clinical potential for evaluating UTUC and detecting lymph node metastasis compared to Ga-68-PSMA-11 PET/CT, likely due to the relatively scant expression of FOLH1 in tumor neovascular endothelium while the abundant expression of GLUT1 in malignancy. Furthermore, the lower neovascular density in UTUC should not be overlooked.