Objectives We aimed to investigate the role of [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT for the initial assessment of gastric cancer and to explore the factors associated with their uptake. Methods This study enrolled 62 patients with histopathologically confirmed gastric cancer. We compared the diagnostic performance of [68Ga]FAPI-04, [18F]FDG, and combined dual-tracer PET/CT. The standardized uptake value (SUV) and tumor-to-background ratio (TBR) were also measured, and the factors that influence tracer uptake were analyzed. Results [68Ga]FAPI-04 PET/CT detected more primary lesions (90.3% vs 77.4%, p = 0.008) and peritoneal metastases (91.7% vs 41.7%, p = 0.031) and demonstrated higher SUVmax and TBR values (p < 0.001) of primary lesions compared to [18F]FDG PET/CT. Dual-tracer PET/CT significantly improved the diagnostic sensitivity for the detection of distant metastases, compared with stand-alone [18F]FDG (97.1% vs 73.5%, p = 0.008) or [68Ga]FAPI-04 (97.1% vs 76.5%, p = 0.016) PET/CT. Subsequently, treatment strategies were changed in nine patients following [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT. Nevertheless, [68Ga]FAPI-04 uptake was primarily influenced by the size and invasion depth of the tumor. Both [68Ga]FAPI-04 and [18F]FDG PET/CT showed limited sensitivity for detecting early gastric cancer (EGC) (37.5% vs 25.0%, p > 0.05). Conclusions In this initial study, [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT were complementary and improved sensitivity for the detection of distant metastases pre-treatment in gastric cancer and could improve treatment stratification in the future. [68Ga]FAPI-04 had limited efficacy in detecting EGC. Key Points •[68Ga]FAPI-04 and[18F]FDG dual-tracer PET/CT are complementary to each other for improving diagnostic sensitivity in the initial evaluation of distant metastases from gastric cancer. •[68Ga]FAPI-04 PET/CT showed limited sensitivity in detecting EGC. • Need for further validation in a larger multi-centre prospective study.

Receptor transporting protein (RTP) family members, RTP1S and RTP2, are accessory proteins to mammalian odorant receptors (ORs). They are expressed in the olfactory sensory neurons and facilitate OR trafficking to the cell-surface membrane and ligand-induced responses in heterologous cells. We previously identified different domains in RTP1S that are important for different stages of OR trafficking, odorant-mediated responses, and interaction with ORs. However, the exact roles of RTP2 and the significance of the requirement of the seemingly redundant co-expression of the two RTP proteins in vivo have received less attention in the past. Here we attempted to dissect the functional differences between RTP1S and RTP2 using a HEK293T cell-based OR heterologous expression system. When a set of 24 ORs were tested against 28 cognate ligands, unlike RTP1S, which always showed a robust ability to support odorant-mediated responses, RTP2 had little or no effect on OR responses and exhibited a suppressive effect over that of RTP1S for a subset of the ORs tested. RTP1S and RTP2 showed no significant difference in OR ligand selectivity and co-transfection with RTP2 increased the detection threshold for some ORs. A protein-protein interaction analysis showed positive interactions among OR, RTP1S, and RTP2, corroborating the functional linkages among the three molecules. Finally, further cell-surface and permeabilized immunocytochemical studies revealed that OR and the co-expressed RTP1S proteins were retained in the Golgi when co-transfected with RTP2, indicating that RTP1S and RTP2 could play different roles in the OR trafficking process. By examining the functional differentiations between the two RTP family members, we provided a molecular level explanation to the suppressive effect exerted by RTP2, shedding light on the divergent mechanisms underlying the RTP proteins in regulating the functional expression of ORs.

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