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

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 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.

Methods: 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.

Results: 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.

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 knowledge: 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.

Keywords: BNCT; L-BPA; Liver malignancies; Preloading; [(18)F]FBPA.