Yoon Hyeun Oum1, Dinesh Shetty2, Younghyoun Yoon1, Zhongxing Liang3, Ronald J Voll2, Mark M Goodman4, Hyunsuk Shim5. 1. Department of Radiation Oncology, Emory University School of Medicine, USA. 2. Department of Radiology and Image Sciences, Emory University School of Medicine, USA. 3. Department of Radiation Oncology, Emory University School of Medicine, USA; Winship Cancer Institute, Atlanta, GA 30322, USA. 4. Department of Radiology and Image Sciences, Emory University School of Medicine, USA; Winship Cancer Institute, Atlanta, GA 30322, USA. 5. Department of Radiation Oncology, Emory University School of Medicine, USA; Department of Radiology and Image Sciences, Emory University School of Medicine, USA; Winship Cancer Institute, Atlanta, GA 30322, USA. Electronic address: hshim@emory.edu.
Abstract
CXCR4 is involved in various diseases such as inflammation, tumor growth, and cancer metastasis through the interaction with its natural endogenous ligand, chemokine CXCL12. In an effort to develop imaging probes for CXCR4, we developed a novel small molecule CXCR4-targeted PET agent (compound 5) by combining our established benzenesulfonamide scaffold with a labeling component by virtue of click chemistry. 5 shows nanomolar affinity (IC50 = 6.9 nM) against a known CXCR4 antagonist (TN14003) and inhibits more than 65% chemotaxis at 10 nM in vitro assays. Radiofluorinated compound 5 ([18F]5) demonstrates a competitive cellular uptake against CXCL12 in a dose-dependent manner. Further, microPET images of [18F]5 exhibits preferential accumulation of radioactivity in the lesions of λ-carrageenan-induced paw edema, human head and neck cancer orthotopic xenograft, and metastatic lung cancer of each mouse model.
CXCR4 is involved in various diseases such as n class="Disease">inflammation, tumor growth, and cancer metastasis through the interaction with its natural endogenous ligand, chemokine CXCL12. In an effort to develop imaging probes for CXCR4, we developed a novel small molecule CXCR4-targeted PET agent (compound 5) by combining our established benzenesulfonamide scaffold with a labeling component by virtue of click chemistry. 5 shows nanomolar affinity (IC50 = 6.9 nM) against a known CXCR4 antagonist (TN14003) and inhibits more than 65% chemotaxis at 10 nM in vitro assays. Radiofluorinated compound 5 ([18F]5) demonstrates a competitive cellular uptake against CXCL12 in a dose-dependent manner. Further, microPET images of [18F]5 exhibits preferential accumulation of radioactivity in the lesions of λ-carrageenan-induced paw edema, humanhead and neck cancer orthotopic xenograft, and metastatic lung cancer of each mouse model.
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