Comparative evaluation of [¹⁸F]FAPI-42 and [¹⁸F]PSMA-1007 PET/CT for lesion detection and uptake in prostate cancer...

Although [¹⁸F]PSMA-1007 enables sensitive detection in prostate cancer, heterogeneity in PSMA expression and variable physiologic uptake can limit performance, whereas [¹⁸F]FAPI-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 [¹⁸F]FAPI-42 and [¹⁸F]PSMA-1007 PET/CT in patients with prostate cancer, and assess lesion detection rates and uptake on [¹⁸F]FAPI-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. [¹⁸F]PSMA-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. [¹⁸F]PSMA-1007 also demonstrated higher SUV_max and TBR_blood than [¹⁸F]FAPI-42 PET/CT for primary/recurrent tumors (SUV_max 15.5 ± 16.8 vs. 4.2 ± 2.2; TBR_blood 13.5 ± 14.0 vs. 3.5 ± 2.9), lymph node (SUV_max 14.9 ± 15.3 vs. 3.8 ± 2.7; TBR_blood 12.8 ± 12.1 vs. 3.5 ± 2.9), bone (SUV_max 11.9 ± 9.4 vs. 6.8 ± 3.5; TBR_blood 13.1 ± 12.1 vs. 6.3 ± 3.5), and visceral metastases (SUV_max 14.6 ± 9.4 vs. 7.8 ± 4.6; TBR_blood 22.8 ± 12.3 vs. 6.9 ± 6.2). Among disease stages, lesion detection rates on [¹⁸F]FAPI-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). SUV_max of lesion on [¹⁸F]FAPI-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 [¹⁸F]FAPI-42, clinical management was altered.

While [¹⁸F]PSMA 1007 PET/CT remains superior for overall lesion detection, [¹⁸F]FAPI 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.