Comparative evaluation of ¹⁸FFAPI-42 and ¹⁸FPSMA-1007 PET/CT for lesion detection and uptake in prostate cancer across disease stages

Although ¹⁸FPSMA-1007 enables sensitive detection in prostate cancer, heterogeneity in PSMA expression and variable physiologic uptake can limit performance, whereas ¹⁸FFAPI-42, targeting fibroblast activation protein in tumor stroma and typically exhibiting low background, may improve conspicuity in regions affected by physiologic PSMA activity and in phenotypes with reduced PSMA expression. This study aimed to compare ¹⁸FFAPI-42 and ¹⁸FPSMA-1007 PET/CT in patients with prostate cancer, and assess lesion detection rates and uptake on ¹⁸FFAPI-42 PET/CT across various disease stages. Of 759 lesions from 55 patients, 187 were PSMA-positive only, 72 were FAPI-positive only, and 500 were positive on both tracers. ¹⁸FPSMA-1007 detected more lesions in newly diagnosed (233 vs. 181, P = 0.0001), biochemical recurrence (BCR) (67 vs. 56, P = 0.04), and castration-resistant prostate cancer(CRPC) (385 vs. 333, P < 0.0001) groups. ¹⁸FPSMA-1007 also demonstrated higher SUVmax and TBRblood than ¹⁸FFAPI-42 PET/CT for primary/recurrent tumors (SUVmax 15.5 ± 16.8 vs. 4.2 ± 2.2; TBRblood 13.5 ± 14.0 vs. 3.5 ± 2.9), lymph node (SUVmax 14.9 ± 15.3 vs. 3.8 ± 2.7; TBRblood 12.8 ± 12.1 vs. 3.5 ± 2.9), bone (SUVmax 11.9 ± 9.4 vs. 6.8 ± 3.5; TBRblood 13.1 ± 12.1 vs. 6.3 ± 3.5), and visceral metastases (SUVmax 14.6 ± 9.4 vs. 7.8 ± 4.6; TBRblood 22.8 ± 12.3 vs. 6.9 ± 6.2). Among disease stages, lesion detection rates on ¹⁸FFAPI-42 were higher in CRPC (84.5%) and BCR (75.7%) than in newly diagnosed cases (62.6%; P < 0.0001 and P = 0.04, respectively). SUVmax of lesion on ¹⁸FFAPI-42 PET/CT were highest in CRPC (6.6 ± 3.9), followed by BCR (5.9 ± 3.7), and newly diagnosed disease (4.3 ± 2.5; P < 0.005). In 3 of 5 patients with discordant findings favoring ¹⁸FFAPI-42, clinical management was altered. While ¹⁸FPSMA 1007 PET/CT remains superior for overall lesion detection, ¹⁸FFAPI 42 PET/CT may provide complementary value in selected scenarios, particularly in subsets with reduced PSMA expression. Chinese Clinical Trial Registry, ChiCTR2200063441. Registered 06 September 2022, https//www.chictr.org.cn/bin/project/edit? pid=149,714.