title: Phase IIa clinical study of [18F]fluciclovine: efficacy and safety of a new PET tracer for brain tumors.
abstract: OBJECTIVE
  [18F]Fluciclovine (anti-[18F]FACBC) has demonstrated diagnostic efficacy for cancers of the brain where [18F]fludeoxyglucose has limitations. We conducted a phase IIa study of anti-[18F]FACBC to assess its accumulation pattern and safety in patients with malignant glioma.
  
  
  METHODS
  Five patients with glioma scheduled for brain tumor resection received anti-[18F]FACBC. Brain positron emission tomography (PET) was performed following intravenous administration of anti-[18F]FACBC, and subsequently, preoperative gadolinium contrast-enhanced T1-weighted (CE-T1W) magnetic resonance imaging (MRI) was performed for surgery. Specimens for histopathological evaluation were collected during surgery, and their location was precisely determined on CE-T1W MRI and anti-[18F]FACBC PET/CT images. In addition, tumor extent defined on the MRI and PET/CT images was compared. To determine time-activity curves for anti-[18F]FACBC uptake in brain tumor and normal tissues, regions of interest were set in the brain tumor, contralateral normal tissue and the cerebellum, and their standardized uptake values (SUV) were calculated. The safety of anti-[18F]FACBC was assessed based on subjective symptoms and objective findings, electrocardiograms, vital signs, laboratory results, and the incidence of adverse events.
  
  
  RESULTS
  Anti-[18F]FACBC accumulated in the malignant gliomas of all patients. CE-T1W MRI detected gliomas in all patients, but anti-[18F]FACBC PET/CT generally delineated wider regions of tumor extent than CE-T1W MRI. Two of the histopathologically confirmed tumors were located in regions that were defined using anti-[18F]FACBC PET/CT, but not using CE-T1W MRI. Two patients experienced three mild adverse events: one complained of a dull headache and later a mild headache, and the other showed general malaise. These symptoms resolved spontaneously without treatment. Only the mild headache could not be ruled out from having a causal relationship with anti-[18F]FACBC. Favorable T/N ratios regarding anti-[18F]FACBC uptake between tumors and normal control tissues were demonstrated in this trial.
  
  
  CONCLUSIONS
  It is suggested that anti-[18F]FACBC PET/CT has the ability to delineate glioma spread that is undetectable using CE-T1W MRI. Anti-[18F]FACBC is safe in patients with malignant glioma. This study was registered in the Japan Pharmaceutical Information Center Clinical Trials Information, which is one of the World Health Organization registries (registration number: JapicCTI-111387).
authors.affiliation: Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. knd-aki@juntendo.ac.jp.
authors.forename: Akihide
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Radiology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Aoki
authors.affiliation: Department of Radiology, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20, Shinsuna, Koto-ku, Tokyo, 136-0075, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Radiology, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20, Shinsuna, Koto-ku, Tokyo, 136-0075, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Nagasawa
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Ryogo
authors.initials: R
authors.lastname: Minamimoto
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Arakawa
authors.affiliation: Clinical Development Department, Nihon Medi-Physics Co., Ltd., 3-4-10, Shinsuna, Koto-ku, Tokyo, 136-0075, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tominaga
authors.affiliation: Department of Neurosurgery, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Arai
mesh_terms: D000328:Adult; D000368:Aged; D001692:Biological Transport; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D002264:Carboxylic Acids / Q000009:adverse effects*; D003503:Cyclobutanes / Q000009:adverse effects*; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D012449:Safety
chemical_list: D002264:Carboxylic Acids; D003503:Cyclobutanes; D011849:Radioactive Tracers; C117460:fluciclovine F-18
keywords: Clinical trial; Glioblastoma; Magnetic resonance imaging; Positron emission tomography; [18F]Fluciclovine