PMID- 27837726 OWN - NLM STAT- MEDLINE DCOM- 20171122 LR - 20180315 IS - 1872-9614 (Electronic) IS - 0969-8051 (Linking) VI - 44 DP - 2017 Jan TI - On the applicability of [(18)F]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. PG - 83-89 LID - S0969-8051(16)30141-X [pii] LID - 10.1016/j.nucmedbio.2016.08.012 [doi] AB - INTRODUCTION: 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 a (10)B-pharmaceutical in liver malignancies. In this work we evaluated in a preclinical tumor model if [(18)F]FBPA tissue distribution measured with PET is able to predict the tissue distribution of [(10)B]L-BPA. METHODS: Tumor bearing mice (hepatocellular carcinoma cell line, HuH-7) were either subject of a [(18)F]FBPA-PET scan with subsequent measurement of radioactivity content in extracted organs using a gamma counter or injected with [(10)B]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 [(18)F]FBPA and [(10)B]L-BPA was evaluated and the pharmacokinetics of [(18)F]FBPA investigated by compartment modeling. RESULTS: We found a significant correlation between [(18)F]FBPA and [(10)B]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 [(18)F]FBPA ranged from 1.2 to 1.5. Preloading did not increase the uptake of [(18)F]FBPA or [(10)B]L-BPA in any organ and compartment modeling showed no statistically significant differences in [(18)F]FBPA tumor kinetics. CONCLUSIONS: [(18)F]FBPA-PET predicts [(10)B]L-BPA concentration after amino acid preloading in HuH-7 hepatocellular carcinoma models. Preloading had no effect on tumor uptake of [(18)F]FBPA. ADVANCES IN KNOWLEDGE: Despite differences in chemical structure and administered dose [(18)F]FBPA and [(10)B]L-BPA demonstrate an equivalent biodistribution in a preclinical tumor model. IMPLICATIONS FOR PATIENT CARE: [(18)F]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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Grunewald, Catrin AU - Grunewald C AD - Institut fur Kernchemie, Johannes Gutenberg-Universitat, Mainz, DE -55128, Germany. FAU - Sauberer, Michael AU - Sauberer M AD - Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria. FAU - Filip, Thomas AU - Filip T AD - Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria. FAU - Wanek, Thomas AU - Wanek T AD - Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria. FAU - Stanek, Johann AU - Stanek J AD - Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria. FAU - Mairinger, Severin AU - Mairinger S AD - Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria. FAU - Rollet, Sofia AU - Rollet S AD - Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria. FAU - Kudejova, Petra AU - Kudejova P AD - Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Universitat Munchen, D-85748, Garching, Germany. FAU - Langer, Oliver AU - Langer O AD - Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. FAU - Schutz, Christian AU - Schutz C AD - Institut fur Kernchemie, Johannes Gutenberg-Universitat, Mainz, DE -55128, Germany. FAU - Blaickner, Matthias AU - Blaickner M AD - Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria. FAU - Kuntner, Claudia AU - Kuntner C AD - Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria. Electronic address: claudia.kuntner@ait.ac.at. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160829 PL - United States TA - Nucl Med Biol JT - Nuclear medicine and biology JID - 9304420 RN - 0 (Boron Compounds) RN - 133921-60-5 (4-borono-2-fluorophenylalanine) RN - 47E5O17Y3R (Phenylalanine) RN - UID84303EL (4-boronophenylalanine) SB - IM MH - Animals MH - Boron Compounds/*metabolism MH - *Boron Neutron Capture Therapy MH - Cell Line, Tumor MH - Female MH - Humans MH - Liver Neoplasms/diagnostic imaging/*metabolism/pathology/*radiotherapy MH - Mice MH - Phenylalanine/*analogs & derivatives/metabolism MH - Positron-Emission Tomography OTO - NOTNLM OT - BNCT OT - L-BPA OT - Liver malignancies OT - Preloading OT - [(18)F]FBPA EDAT- 2016/11/13 06:00 MHDA- 2017/11/29 06:00 CRDT- 2016/11/13 06:00 PHST- 2016/05/13 00:00 [received] PHST- 2016/08/25 00:00 [revised] PHST- 2016/08/26 00:00 [accepted] PHST- 2016/11/13 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2016/11/13 06:00 [entrez] AID - S0969-8051(16)30141-X [pii] AID - 10.1016/j.nucmedbio.2016.08.012 [doi] PST - ppublish SO - Nucl Med Biol. 2017 Jan;44:83-89. doi: 10.1016/j.nucmedbio.2016.08.012. Epub 2016 Aug 29.