| Autor: |
Luo Y; Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China., Jin W; Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China., Zang J; Department of Nuclear Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China., Wang G; Department of Nuclear Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China., Zhu L; Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China., Kung HF; Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States. |
| Abstrakt: |
Fibroblast activation protein (FAP), which is overexpressed in cancer-associated fibroblasts (CAFs), represents a promising target for cancer diagnosis and therapy. Hypoxia is a common feature of solid tumors. A bivalent agent, DOTA-NI-FAPI-04 ( 1 ), was developed by incorporating hypoxia-sensitive nitroimidazole (NI) into the FAP-targeting agent FAPI-04. Compound 1 exhibited a strong FAP binding affinity with an IC 50 of 7.44 nM. Radiolabeled [ 68 Ga]Ga- 1 and [ 177 Lu]Lu- 1 demonstrated enhanced in vitro cell uptake. In vivo positron emission tomography/computed tomography (PET/CT) imaging showed that [ 68 Ga]Ga- 1 displayed significantly higher specific uptake and retention in U87MG tumor-bearing mice compared to [ 68 Ga]Ga-FAPI-04 (SUV avg : 7.87 vs 1.99% ID/mL at 120 min). Biodistribution studies confirmed superior tumor uptake of [ 68 Ga]Ga- 1 (48.15 vs 5.72% ID/g at 120 min). Similarly, [ 177 Lu]Lu- 1 exhibited higher tumor uptake than [ 177 Lu]Lu-FAPI-04 (50.75 vs 20.48% ID/g at 120 min). These preliminary results suggest that a nitroimidazole-containing bivalent-targeting agent, [ 68 Ga]Ga/[ 177 Lu]Lu- 1 , is a promising candidate for tumor theranostics. |
