Abstract
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Introduction: Fibroblast activation protein has been an attractive target for tumor diagnosis and therapy. There have been many successful clinical transformations with small molecules and peptides. The antibody has a longer blood half-life and better tumor retention than small molecules. However, only a few anti-FAP antibody diagnostic or therapeutic agents were reported in recent years. In this study, an anti-FAP antibody was developed to be the nuclear medicine with 177Lu for FAP therapy.
Methods: The anti-FAP antibody was labeled with 89Zr for longitudinal PET/CT imaging in NU/NU mice bearing HT1080-FAP tumor models for two weeks. Three different chelators conjugated with antibody were compared by stability analysis and SPECT imaging. SPECT imaging in FAP positive and negative tumor models, biodistribution study and radiotherapy study were performed with177Lu labeled anti-FAP antibody.
Results: The uptake of tumor in 89Zr PET imaging was increasing with time， the highest SUVmax of tumor was 18.36±2.28 at 192 h post-injection. The uptake in liver and blood was decreasing with time, the highest SUV of the liver was 2.07±0.31 at 1 h post-injection. It showed that there was no uptake in negative tumor models in SPECT imaging. The tumor uptake were 23.04±5.11% ID/g，33.2±6.36% ID/g，19.87±6.84% ID/g，19.02±5.90 % ID/g at 1，4，7，10 days after injection in biodistribution study. In the radiotherapy study, 3.7 MBq, 7.4 MBq, 11.1 MBq, 18.5 MBq 177Lu labeled anti-FAP antibody and anti-FAP antibody were used as therapy groups. Even 3.7 MBq 177Lu labeled anti-FAP antibody revealed complete remission of tumors compared with the antibody group and control group.
Conclusions: Nuclear medicine imaging and radiotherapy results showed that this anti-FAP antibody was FAP specific and had low background uptake. The excellent therapy effect will fill the gap in the treatment of FAP positive tumors.
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