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

• Published in: Nuclear medicine and biology 2017-01, Vol.44, p.83-89
• Main Authors: Grunewald, Catrin, Sauberer, Michael, Filip, Thomas, Wanek, Thomas, Stanek, Johann, Mairinger, Severin, Rollet, Sofia, Kudejova, Petra, Langer, Oliver, Schütz, Christian, Blaickner, Matthias, Kuntner, Claudia
• Format: Article
• Language: English
• Subjects: [18F]FBPA; Animals; BNCT; Boron Compounds - metabolism; Boron Neutron Capture Therapy; Cell Line, Tumor; Female; Humans; L-BPA; Liver malignancies; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - radiotherapy; Mice; Phenylalanine - analogs & derivatives; Phenylalanine - metabolism; Positron-Emission Tomography; Preloading; Radiology
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2016.08.012

Abstract 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 a10 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 modelling. 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 modelling 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.