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

Abstract

BackgroundBoron neutron capture therapy (BNCT) is a molecular radiation treatment based on the 10B (n, α) 7Li nuclear reaction in cancer cells, in which delivery of 10B 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.MethodsRGC-6 rat glioma cells (1.9 × 107) 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 10B in the autopsied tissues and blood was measured by inductively coupled plasma optical emission spectrometry (ICP-OES).ResultsThe highest absolute concentration of 10B 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).ConclusionsFBPA PET can reliably predict accumulation of BPA-fr in the tumor as well as normal tissues.

Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy

“…First, organs that include air such as the intestine and lung could be evaluated without underestimation by the same protocol in both the L-BPA group and [ 19 F]-L-FBPA group in this study. In particular, [ 18 F]-L-FBPA accumulation in hollow organs or the lung is significantly underestimated by PET based on the maximum or average counts [16]. In this study, the boron concentrations of the intestine and lung showed no significant difference between the L-BPA group and [ 19 F]-L-FBPA group.…”

“…Previous studies have compared the radioactivity accumulation of [ 18 F]-L-FBPA in tumour and normal tissues by PET as well as the boron concentrations of L-BPA in tumour and normal tissues by ICP-AES [16, 20, 21]. Ishiwata and colleagues examined the effect of L-BPA loading on the uptake of [ 18 F]-L-FBPA by measuring the radioactivity of 18 F in B16 melanoma-bearing mice [20].…”

“…Regarding tumour tissue, Imahori showed that the boron level in the tumour tissue estimated with [ 18 F]-L-FBPA PET method was closed to that of surgical specimens directly measured after a single injection of L-BPA with the prompt gamma method [15]. Regarding normal tissue, Hanaoka and colleagues demonstrated that each PET parameter of normal tissue after a tracer-dose single injection of [ 18 F]-L-FBPA showed good correlation with the boron concentrations of normal tissue measured by ICP-AES after a single injection of L-BPA [16]. However, there are no previous reports that compare the difference of boron accumulation in tissues between [ 18 F]-L-FBPA and L-BPA under the same injection dose, the same administration protocol, and the same boron measurement protocol.…”

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

“…Our animal studies demonstrated that 18 F‐FBPA uptake was significantly associated with boron concentration in 6 tumors, despite the fact that the administered dose of 18 F‐FBPA is different from that of BPA. Hanaoka et al recently revealed an association between BPA and 18 F‐FBPA uptakes by bolus injection in RGC‐6 rat glioma and normal tissues. Wang et al also demonstrated that tumor uptake of BPA or 18 F‐FBPA reached maximum levels at 1 hour following bolus injection, which indicated their similar pharmacokinetics.…”

Poly(vinyl alcohol) boosting therapeutic potential of p -boronophenylalanine in neutron capture therapy by modulating metabolism

“…BPA has the structure of phenylalanine that can be recognized mainly by LAT1 amino acid transporters overexpressed on many cancer cells, thereby permitting efficient cellular internalization (5,6). In addition, fluorinated BPA ( 18 F-BPA) was recently developed for companion diagnostics, and it has been experimentally demonstrated that 18 F-BPA exhibits similar biodistribution to the unfluorinated BPA (7,8) and allows us to quantitatively illustrate tumor accumulation of BPA and select patients who are likely to receive benefit from BNCT (9).…”