title: On the applicability of [18F]FBPA to predict L-BPA concentration after amino acid preloading in HuH-7 liver tumor model and the implication for liver boron neutron capture therapy.
abstract: In recent years extra-corporal application of boron neutron capture therapy (BNCT) was evaluated for liver primary tumors or liver metastases. A prerequisite for such a high-risk procedure is proof of preferential delivery and high uptake of a10B-pharmaceutical in liver malignancies. In this work we evaluated in a preclinical tumor model if [18F]FBPA tissue distribution measured with PET is able to predict the tissue distribution of [10B]L-BPA.
  
  
  
  Tumor bearing mice (hepatocellular carcinoma cell line, HuH-7) were either subject of a [18F]FBPA-PET scan with subsequent measurement of radioactivity content in extracted organs using a gamma counter or injected with [10B]L-BPA with tissue samples analyzed by prompt gamma activation analysis (PGAA) or quantitative neutron capture radiography (QNCR). The impact of L-tyrosine, L-DOPA and L-BPA preloading on the tissue distribution of [18F]FBPA and [10B]L-BPA was evaluated and the pharmacokinetics of [18F]FBPA investigated by compartment modeling.
  
  
  
  We found a significant correlation between [18F]FBPA and [10B]L-BPA uptake in tumors and various organs as well as high accumulation levels in pancreas and kidneys as reported in previous studies. Tumor-to-liver ratios of [18F]FBPA ranged from 1.2 to 1.5. Preloading did not increase the uptake of [18F]FBPA or [10B]L-BPA in any organ and compartment modeling showed no statistically significant differences in [18F]FBPA tumor kinetics.
  
  
  
  [18F]FBPA-PET predicts [10B]L-BPA concentration after amino acid preloading in HuH-7 hepatocellular carcinoma models. Preloading had no effect on tumor uptake of [18F]FBPA.
  
  
  
  Despite differences in chemical structure and administered dose [18F]FBPA and [10B]L-BPA demonstrate an equivalent biodistribution in a preclinical tumor model. IMPLICATIONS FOR PATIENT CARE: [18F]FBPA-PET is suitable for treatment planning and dose calculations in BNCT applications for liver malignancies. However, alternative tracers with more favorable tumor-to-liver ratios should be investigated.
authors.affiliation: Institut für Kernchemie, Johannes Gutenberg-Universität, Mainz, DE -55128, Germany.
authors.forename: Catrin
authors.initials: C
authors.lastname: Grunewald
authors.affiliation: Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Sauberer
authors.affiliation: Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Filip
authors.affiliation: Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wanek
authors.affiliation: Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Stanek
authors.affiliation: Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria.
authors.forename: Severin
authors.initials: S
authors.lastname: Mairinger
authors.affiliation: Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria.
authors.forename: Sofia
authors.initials: S
authors.lastname: Rollet
authors.affiliation: Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Universität München, D-85748, Garching, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Kudejova
authors.affiliation: Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Langer
authors.affiliation: Institut für Kernchemie, Johannes Gutenberg-Universität, Mainz, DE -55128, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schütz
authors.affiliation: Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blaickner
authors.affiliation: Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria. Electronic address: claudia.kuntner@ait.ac.at.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kuntner
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000378:metabolism*; D016754:Boron Neutron Capture Therapy; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D049268:Positron-Emission Tomography
chemical_list: D001896:Boron Compounds; C072915:4-borono-2-fluorophenylalanine; D010649:Phenylalanine; C033685:4-boronophenylalanine
keywords: BNCT; L-BPA; Liver malignancies; Preloading; [(18)F]FBPA