title: Evaluation of trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid accumulation in low-grade glioma in chemically induced rat models: PET and autoradiography compared with morphological images and histopathological findings.
abstract: BACKGROUND
  Magnetic resonance imaging (MRI) can have a problem to delineate diffuse gliomas with an intact blood-brain barrier (BBB) especially when a marked peritumoral edema is present. We evaluated the potential of trans-1-amino-3-(18)F-fluorocyclobutanecarboxylic acid (anti-(18)F-FACBC) positron emission tomography (PET) to delineate the extent of diffuse gliomas by comparing PET findings with autoradiography, in vivo and ex vivo MRI, and histopathology findings.
  
  
  METHODS
  Dynamic PET was performed in rats with N-ethyl-N-nitrosourea-induced glioma for 60 min after anti-(18)F-FACBC injection. Contrast-enhanced MRI was performed before or after PET. The PET images were fused with in vivo and ex vivo MR images, and histopathological images for direct comparisons. Autoradiograms were compared with the results of Evans Blue (EB) extravasation (to assess BBB integrity) and hematoxylin-eosin staining.
  
  
  RESULTS
  Histopathological examination, including EB extravasation assessment, and enhanced T1-weighted MRI identified several diffuse gliomas with slight BBB disruption, similar to low-grade human gliomas. Anti-(18)F-FACBC uptake was specific and high in the gliomas, irrespective of BBB integrity. Higher anti-(18)F-FACBC uptake corresponded to areas of T2 hyperintensity, independent of gadolinium enhancement. Ex vivo autoradiography also showed high anti-(18)F-FACBC accumulation in tumors lacking EB extravasation and a correlation between anti-(18)F-FACBC accumulation and tumor cell density, but not EB extravasation.
  
  
  CONCLUSIONS
  Anti-(18)F-FACBC-PET allowed visualization of gliomas irrespective of BBB integrity. The tumor-to-normal uptake ratio of anti-(18)F-FACBC generally correlated with the relative cell density. Anti-(18)F-FACBC PET combined with MRI shows promise for preoperative glioma delineation.
  
  
  CONCLUSIONS
  Radiopharmaceuticals that cross the BBB, such as anti-(18)F-FACBC, are taken up by low-grade gliomas with equivocal MRI findings due to an intact BBB.
  
  
  CONCLUSIONS
  Surgery is the first-line therapy for low-grade gliomas; therefore, delineation of their extent in the presence of an intact BBB is essential to planning surgery that removes the entire neoplasm, which will positively affect long-term survival.
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba, Japan. Electronic address: yoshihiro_doi@nmp.co.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Doi
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kanagawa
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Maya
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Oka
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Nakata
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Toyama
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Shirakami
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D001932:Brain Neoplasms / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology; D002264:Carboxylic Acids / Q000493:pharmacokinetics*; D003503:Cyclobutanes / Q000493:pharmacokinetics*; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D005910:Glioma / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D060787:Neoplasm Grading; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: D000477:Alkylating Agents; D002264:Carboxylic Acids; D003503:Cyclobutanes; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C117460:fluciclovine F-18; D005038:Ethylnitrosourea
keywords: Anti-(18)F-FACBC; Blood–Brain barrier; Glioma; Magnetic resonance imaging; Positron emission tomography