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.
Keywords: 18F-FAPI-42-RGD; PET imaging; dual-targeting tracer; fibroblast activation protein; gastric cancer; integrin αvβ3.
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