FBPA PET in boron neutron capture therapy for cancer: prediction of (10)B concentration in the tumor and normal tissue in a rat xenograft model

Kohei Hanaoka; Tadashi Watabe; Sadahiro Naka; Yasukazu Kanai; Hayato Ikeda; Genki Horitsugi; Hiroki Kato; Kayako Isohashi; Eku Shimosegawa; Jun Hatazawa

doi:10.1186/s13550-014-0070-2

FBPA PET in boron neutron capture therapy for cancer: prediction of (10)B concentration in the tumor and normal tissue in a rat xenograft model

EJNMMI Res. 2014 Dec 20;4(1):70. doi: 10.1186/s13550-014-0070-2. eCollection 2014 Dec.

Authors

Affiliations

¹ Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Japan.
² Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Suita, Japan ; PET Molecular Imaging Center, Osaka University Graduate School of Medicine, Suita, Japan.
³ Osaka University Hospital, Suita, Japan.
⁴ Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Japan ; PET Molecular Imaging Center, Osaka University Graduate School of Medicine, Suita, Japan.
⁵ Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Japan ; PET Molecular Imaging Center, Osaka University Graduate School of Medicine, Suita, Japan ; Immunology Frontier Research Center, Osaka University, Suita, Japan.

Abstract

Background: Boron neutron capture therapy (BNCT) is a molecular radiation treatment based on the (10)B (n, α) (7)Li nuclear reaction in cancer cells, in which delivery of (10)B by 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is of critical importance. The PET tracer 4-borono-2-(18) F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. However, because of the difference in chemical structure between BPA-fr and FBPA and the difference in the dose administered between BPA-fr (therapeutic dose) and FBPA (tracer dose), the predictive value of FBPA PET for BPA-fr accumulation in the tumor and normal tissues is not yet clearly proven. We conducted this study to validate FBPA PET as a useful test to predict the accumulation of BPA-fr in the tumor and normal tissues before BNCT.

Methods: RGC-6 rat glioma cells (1.9 × 10(7)) were implanted subcutaneously in seven male F344 rats. On day 20 after the tumor implantation, dynamic PET scan was performed on four rats after injection of FBPA for 1 h. Whole-body PET/CT was performed 1 h after intravenous injection of the FBPA solution (30.5 ± 0.7 MBq, 1.69 ± 1.21 mg/kg). PET accumulation of FBPA in the tumor tissue and various normal tissues was estimated as a percentage of the injected dose per gram (%ID/g). One hour after the PET/CT scan, BPA-fructose (167.32 ± 18.65 mg/kg) was injected intravenously, and the rats were dissected 1 h after the BPA-fr injection. The absolute concentration of (10)B in the autopsied tissues and blood was measured by inductively coupled plasma optical emission spectrometry (ICP-OES).

Results: The highest absolute concentration of (10)B determined by ICP-OES was found in the kidney (4.34 ± 0.84 %ID/g), followed by the pancreas (2.73 ± 0.63 %ID/g), and the tumor (1.44 ± 0.44 %ID/g). A significant positive correlation was found between the accumulation levels of BPA-fr and FBPA (r = 0.91, p < 0.05).

Conclusions: FBPA PET can reliably predict accumulation of BPA-fr in the tumor as well as normal tissues.

Keywords: BPA-fr; Boron concentration; Boron nuclear capture therapy; FBPA.