Abstract
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Objectives: Near-infrared (NIR) probe indocyanine green (ICG) is an FDA-approved intraoperative imaging agent to determining cardiac output, hepatic function and liver blood flow. And it has been reported for high local spatial and temporal resolution imaging of hepatocellular carcinomas (HCC)[1-3]. However, the clinical application of ICG for HCC imaging is hampered by the limited penetration depth of NIR fluorescence imaging technology. To overcome this drawback, we designed and synthesized an 18F labeled ICG analogue as a dual-modality imaging probe that could be used for the initial screening of cancer patients with whole-body positron emission tomography (PET) imaging and subsequent intraoperative excision of HCC.
Methods: The desired probe was prepared by conjugation of 3-fluoro[18F]-propylamine to an ICG analogue (sodium 4-[2-[2-[2-chloro-3-[2-[1,1-dimethyl-3-(4-sulfonatobutyl)benzo[e]indol-3-ium-2-yl]ethenyl]cyclopent-2-en-1-ylidene]ethylidene]-1,1-dimethylbenzo[e]indol-3-yl]butane-1-sulfonate). NIR optical imaging evaluation and PET imaging studies were performed in rats bearing HCCs that were chemically induced by diethylnitrosamine (DEN).
Results: The radiolabeling of the ICG analogue with 18F was accomplished with 50% radiochemical yield and over 95% radiochemical purity. Its 19F counterpart, the reference standard, was synthesized and injected into rats with confirmed liver tumors by magnetic resonance imaging (MRI). Optical imaging was performed using an IVIS® Spectrum in reflection mode (excitation 710 nm, emission 800 nm) 24 hours post injection. Small hepatic tumors showed higher fluorescent signals than the background liver tissue, while no fluorescence was observed from other major organs such as kidneys or spleen. Necrotic tumors showed no uptake of the compound. Conclusions: An 18F radiolabeled ICG tracer was successfully designed and synthesized. The optical imaging evaluation performed with its reference standard demonstrated that the fluorinated ICG analog maintained the preferential accumulation of ICG in the liver tumors, which warrants our further optimization of this class of dual-modality agents for imaging-guided therapy of HCCs. Research Support: This project was partially supported by a grant from the Cancer Prevention and Research Institute of Texas (RP110771) and the Dr. Jack Krohmer Professorship Funds.