title: Clinical Translation of an Albumin-Binding PET Radiotracer 68Ga-NEB.
abstract: Suitably labeled Evans blue dye has been successfully applied to evaluate cardiac function, vascular permeability, and lymphatic imaging in preclinical settings. This study documented the first-in-human application of 68Ga-1,4,7-triazacyclononane-N,N',N″-triacetic acid (NOTA)-NEB.
  
  
  METHODS
  The NOTA-conjugated truncated form of Evans blue, NEB, was labeled with 68Ga and tested in BALB/C mice for dynamic PET and ex vivo biodistribution studies. Three healthy volunteers (2 men and 1 woman) underwent 90-min whole-body dynamic PET. The absorbed doses for major organs and whole body were calculated using OLINDA/EXM software. Eleven patients with focal hepatic lesions diagnosed by enhanced CT or MR imaging were subjected to whole-body PET/CT acquisitions at 30 min after intravenous injection of 111-148 MBq (3-4 mCi) of 68Ga-NEB.
  
  
  RESULTS
  NEB dye was labeled with 68Ga (half-time, 68 min) with high yield and purity. After intravenous injection, 68Ga-NEB formed a complex with serum albumin, thus most of the radioactivity was retained in blood circulation. The tracer was demonstrated to be safe in both healthy volunteers and recruited patients without side effects or allergies. Among the 11 patients, hemangiomas showed much higher 68Ga-NEB signal intensity than the surrounding normal hepatic tissues, whereas no apparent difference between lesions and hepatic tissues was identified on 18F-FDG PET. All other focal hepatic lesions including hepatocellular carcinoma, hepatic cysts, and neuroendocrine tumor liver metastases showed negative 68Ga-NEB contrast to hepatic tissues.
  
  
  CONCLUSIONS
  As a blood-pool imaging agent, 68Ga-NEB is safe to use in the clinic, and our preliminary studies demonstrate the value of differentiating hepatic hemangioma from other benign or malignant focal hepatic lesions. Easy labeling with different positron emitters of various half-lives, excellent pharmacokinetics, and imaging quality warrant further clinical applications of NEB-based PET tracers.
authors.affiliation: Department of Nuclear Medicine, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Beijing, China; and Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland.
authors.forename: Lixin
authors.initials: L
authors.lastname: Lang
authors.affiliation: Department of Nuclear Medicine, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Beijing, China; and.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Nuclear Medicine, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Beijing, China; and lifang@pumch.cn shawn.chen@nih.gov.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland.
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland lifang@pumch.cn shawn.chen@nih.gov.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000818:Animals; D056831:Coordination Complexes / Q000493:pharmacokinetics*; D017357:Cyclotrons; D003937:Diagnosis, Differential; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008107:Liver Diseases / Q000175:diagnosis / Q000000981:diagnostic imaging; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D051598:Whole Body Imaging
chemical_list: C000603981:68Ga-1,4,7-triazacyclononane-N,N',N''-triacetic acid; D000418:Albumins; D056831:Coordination Complexes; D019275:Radiopharmaceuticals
keywords: albumin; blood pool; first-in-human; hemangioma; truncated Evans blue