Evaluation of 18F-FAPI-42-RGD as a novel dual-targeting PET tracer in gastric cancer xenograft models.

Abstract

Objective: The heterogeneity of gastric cancer (GC) poses significant challenges for the detection capabilities of monomeric fibroblast activation protein inhibitor (FAPI) tracers, particularly in cases with low FAP expression. To address this limitation, a dual-target heterodimeric radiotracer, ¹⁸F-FAPI-42-RGD, was designed to target both FAP and integrin αvβ3. This study aimed to evaluate the efficacy of ¹⁸F-FAPI-42-RGD in GC models and compare its performance with the mono-specific radiotracer, ¹⁸F-FAPI-42.

Methods: ¹⁸F-FAPI-42-RGD was synthesized, and its radiochemical properties and stability were assessed. Micro-PET imaging and biodistribution studies were conducted in BALB/C nude mice bearing MKN-45, N87-18.2, NUGC4 tumors, and GC patient-derived xenografts (PDX). The results were compared with those obtained from ¹⁸F-FAPI-42.

Results: ¹⁸F-FAPI-42-RGD demonstrated excellent stability in saline and fetal bovine serum (FBS) for at least 2 hours. Compared to ¹⁸F-FAPI-42, ¹⁸F-FAPI-42-RGD exhibited significantly enhanced tumor uptake in MKN-45, N87-18.2, NUGC4, and GC-PDX tumors at all time points. Biodistribution studies revealed that ¹⁸F-FAPI-42-RGD had markedly higher tumor uptake in GC models compared to ¹⁸F-FAPI-42, particularly in the MKN-45, N87-18.2, and GC-PDX tumor models. The uptake of ¹⁸F-FAPI-42-RGD in these tumors was significantly greater than that of ¹⁸F-FAPI-42 (4.97 ± 1.36 vs. 2.18 ± 1.26, 7.02 ± 0.97 vs. 2.34 ± 0.11, and 4.49 ± 1.29 vs. 1.09 ± 0.46 %ID/g in MKN-45, N87-18.2, and GC-PDX, respectively, at 4 h post-injection).

Conclusion: The dual-targeting PET tracer ¹⁸F-FAPI-42-RGD demonstrated significantly enhanced tumor uptake in GC models, along with a clearer background compared to ¹⁸F-FAPI-42. This indicates its superior diagnostic performance, suggesting its potential for clinical translation in the imaging and diagnosis of GC.