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// Ido D. Weiss 1 , Lyn M. Huff 2 , Moses O. Evbuomwan 3 , Xin Xu 1 , Hong Duc Dang 1 , Daniel S. Velez 1 , Satya P. Singh 1 , Hongwei H. Zhang 1 , Paul J. Gardina 4 , Jae-Ho Lee 5 , Liza Lindenberg 6 , Timothy G. Myers 4 , Chang H. Paik 5 , David S. Schrump 7 , Stefania Pittaluga 3 , Peter L. Choyke 6 , Tito Fojo 2 and Joshua M. Farber 1 1 Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA 2 Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 3 Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 4 Genomic Technologies Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA 5 Radiopharmaceutical Laboratory, Nuclear Medicine Division, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA 6 Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 7 Thoracic Epigenetics Section, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Correspondence to: Joshua M. Farber, email: // Keywords : CXCR4, cancer, PET, plerixafor, adrenal Received : December 21, 2016 Accepted : June 16, 2017 Published : August 04, 2017 Abstract Expression of the chemokine receptor CXCR4 by many cancers correlates with aggressive clinical behavior. As part of the initial studies in a project whose goal was to quantify CXCR4 expression on cancers non-invasively, we examined CXCR4 expression in cancer samples by immunohistochemistry using a validated anti-CXCR4 antibody. Among solid tumors, we found expression of CXCR4 on significant percentages of major types of kidney, lung, and pancreatic adenocarcinomas, and, notably, on metastases of clear cell renal cell carcinoma and squamous cell carcinoma of the lung. We found particularly high expression of CXCR4 on adrenocortical cancer (ACC) metastases. Microarrays of ACC metastases revealed correlations between expression of CXCR4 and other chemokine system genes, particularly CXCR7/ACKR3 , which encodes an atypical chemokine receptor that shares a ligand, CXCL12, with CXCR4. A first-in-human study using 64 Cu-plerixafor for PET in an ACC patient prior to resection of metastases showed heterogeneity among metastatic nodules and good correlations among PET SUVs, CXCR4 staining, and CXCR4 mRNA. Additionally, we were able to show that CXCR4 expression correlated with the rates of growth of the pulmonary lesions in this patient. Further studies are needed to understand better the role of CXCR4 in ACC and whether targeting it may be beneficial. In this regard, non-invasive methods for assessing CXCR4 expression, such as PET using 64 Cu-plerixafor, should be important investigative tools.