Fibroblast activation protein (FAP) emerges as a highly promising target for cancer diagnostic imaging and targeted radionuclide therapy. To exploit the therapeutic potential of current FAP inhibitors (FAPIs), this study presented the design and synthesis of a series of FAPI dimers to increase tumor uptake and retention. Preclinical evaluation and a pilot clinical PET imaging study were conducted to screen the lead compound with the potential for radionuclide therapy.

Three new FAPI dimers were synthesized by linking two quinoline-based FAPIs with different spacers. The in vitro binding affinity and preclinical small animal PET imaging of the compounds were compared with their monomeric counterparts, FAPI-04 and FAPI-46. The lead compound, 68Ga-LNC1013, was then evaluated in a pilot clinical PET imaging study involving seven patients with gastrointestinal cancer.

Inclusion Criteria:

1. Histologically and/or clinically confirmed and/or suspicious of gastrointestinal cancer.
2. Signed informed consent.

Exclusion Criteria:

1. pregnancy;
2. breastfeeding;
3. any medical condition that in the opinion of the investigator may significantly interfere with study compliance.

Claustrophobia (unable to accept PET/CT scanning)