Non‐invasive estimation of ¹⁰B‐4‐borono‐L‐phenylalanine‐derived boron concentration in tumors by PET using 4‐borono‐2‐¹⁸F‐fluoro‐phenylalanine

Abstract

In boron neutron capture therapy (BNCT), 10B‐4‐borono‐L‐phenylalanine (BPA) is commonly used as a 10B carrier. PET using 4‐borono‐2‐18F‐fluoro‐phenylalanine (18F‐FBPA PET) has been performed to estimate boron concentration and predict the therapeutic effects of BNCT; however, the association between tumor uptake of 18F‐FBPA and boron concentration in tumors remains unclear. The present study investigated the transport mechanism of 18F‐FBPA and BPA, and evaluated the utility of 18F‐FBPA PET in predicting boron concentration in tumors. The transporter assay revealed that 2‐aminobicyclo‐(2.2.1)‐heptane‐2‐carboxylic acid, an inhibitor of the L‐type amino acid transporter, significantly inhibited 18F‐FBPA and 14C‐4‐borono‐L‐phenylalanine (14C‐BPA) uptake in FaDu and LN‐229 human cancer cells. 18F‐FBPA uptake strongly correlated with 14C‐BPA uptake in 7 human tumor cell lines (r = .93; P < .01). PET experiments demonstrated that tumor uptake of 18F‐FBPA was independent of the administration method, and uptake of 18F‐FBPA by bolus injection correlated well with BPA uptake by continuous intravenous infusion. The results of this study revealed that evaluating tumor uptake of 18F‐FBPA by PET was useful for estimating 10B concentration in tumors.

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

“…All cells were maintained at 37°C in a humidified incubator containing 5% CO 2 and were washed with phosphate-buffered saline (PBS) and harvested with trypsin as necessary. LAT1 expression of these cells were confirmed in previous studies [16,23].…”

Boron neutron capture therapy: Current status and future perspectives

“…The functions of the different transporters (ATB 0,+ , LAT1, and LAT2) in BPA uptake has been evaluated by high-performance liquid chromatography [19]. Furthermore, (18)F-BPA is also a substrate of LAT1 and shows comparable transport ability with BPA into the tumors, and tissue boron concentration of BPA can be quantitatively estimated using L-[(18)F]BPA/PET [20][21][22][23].…”

Development of an Imaging Technique for Boron Neutron Capture Therapy

“…Moreover, differences arising from the type of 18 FBPA administration method used were studied. Yoshimoto and colleagues compared the pharmacokinetics of 18 FBPA administered by bolus intravenous injection and continuous intravenous injection using various tumor models, including glioma cells, and found a correlation between the uptake of 18 FBPA to the tumor administered by bolus and continuous injection methods [12].…”

“…The calculation of the 10 B concentration based on 18 FBPA PET data has not yet been completely resolved. Certainly, some animal studies have revealed that the 10 B concentration arising from a therapeutic dose can be predicted using PET and that the results for intravenous bolus and continuous injection are correlated [9,12], and the 10 B concentration in normal tissue can be predicted using a kinetic analysis in humans [18]. However, some concerns remain regarding how accurately a small amount of 18 FBPA accumulation can reflect the 10 B concentration of BPA in the tumor and surrounding normal tissues when a continuous injection for 1 h or more is performed in humans.…”