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

IntroductionIn 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 10B-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.MethodsTumor 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.ResultsWe 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.Conclusions[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.Advances in knowledgeDespite 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.