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- W2231055772 abstract "1038 Objectives Fibroblast activation protein alpha (FAP) is a serine protease that is overexpressed on neuroepithelial and sarcoma tumors (1-2). The goal of this work was to characterize 89Zr-DFO-F19 mAb, a PET radiopharmaceutical that specifically targets FAP, and evaluate its potential as a PET and Cerenkov Luminescence Imaging (CLI) agent for FAP positive tumors in vivo. Methods 89Zr-DFO-F19 was prepared according to standard protocols (3). The immunoreactivity and Ka of 89Zr-DFO-F19 was determined using the Lindmo Method and the U87mg cell line, which demonstrates the highest endogenous FAP expression among available cancer cell lines. Biodistribution, CLI, small animal PET/CT and autoradiography studies were conducted in mice bearing FAP+ U87mg tumors using known procedures. Results 89Zr-DFO-F19 was radiolabeled in high radiochemical purity and with a specific activity of 158.3 ± 1.6 MBq/mg (4.28 ± 0.04 mCi / mg, n = 6). CLI imaging of female nude mice implanted with U87mg tumors in the flank revealed substantially greater uptake in tumors than in other tissues such as liver, kidney, muscle or bone. Small animal PET/CT image analysis revealed excellent tumor accumulation of the radiopharmaceutical at 48 h p.i., which was reduced upon the administration of blockade [tumor: (non-block vs. block: SUV; p value): 2.39±0.45 vs. 1.73 ±0.11; 0.03]. Autoradiography and histological analysis of tissue slices demonstrated the colocalization of radioactivity with areas of increased FAP expression and validated both the CLI and small animal PET/CT results. Conclusions 89Zr-DFO-F19 represents a novel PET radiopharmaceutical for FAP positive tumors. CLI imaging confirmed localization within tumor xenografts but not in FAP negative tissues. This was corroborated by biodistribution, small animal PET/CT and autoradiography studies. Research Support DoD W81XWH-13-1-0125" @default.
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- W2231055772 date "2014-05-01" @default.
- W2231055772 modified "2023-09-22" @default.
- W2231055772 title "Imaging fibroblast activation protein alpha expression using 89Zr-DFO-F19 mAb" @default.
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