A Dual Reporter Iodinated Labeling Reagent for Cancer Positron Emission Tomography Imaging and Fluorescence-Guided Surgery

• Published in: Journal of medicinal chemistry 2018-02, Vol.61 (4), p.1636-1645
• Main Authors: Lu, Zhi, Pham, Truc Thuy, Rajkumar, Vineeth, Yu, Zilin, Pedley, R Barbara, Årstad, Erik, Maher, John, Yan, Ran
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - chemistry; Heterografts; Humans; Immunoconjugates - chemistry; Iodine Radioisotopes - chemistry; Mice; Neoplasms - diagnostic imaging; Neoplasms - surgery; Optical Imaging; Positron-Emission Tomography - methods
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.7b01746

The combination of early diagnosis and complete surgical resection offers the greatest prospect of curative cancer treatment. An iodine-124/fluorescein-based dual-modality labeling reagent, 124I-Green, constitutes a generic tool for one-step installation of a positron emission tomography (PET) and a fluorescent reporter to any cancer-specific antibody. The resulting antibody conjugate would allow both cancer PET imaging and intraoperative fluorescence-guided surgery. 124I-Green was synthesized in excellent radiochemical yields of 92 ± 5% (n = 4) determined by HPLC with an improved one-pot three-component radioiodination reaction. The A5B7 carcinoembryonic antigen (CEA)-specific antibody was conjugated to 124I-Green. High tumor uptake of the dual-labeled A5B7 of 20.21 ± 2.70, 13.31 ± 0.73, and 10.64 ± 1.86%ID/g was observed in CEA-expressing SW1222 xenograft mouse model (n = 3) at 24, 48, and 72 h post intravenous injection, respectively. The xenografts were clearly visualized by both PET/CT and ex vivo fluorescence imaging. These encouraging results warrant the further translational development of 124I-Green for cancer PET imaging and fluorescence-guided surgery.