Abstract
ObjectiveBoron neutron capture therapy (BNCT) is a noninvasive radiation therapy method for cancer treatment. In BNCT, 4-borono-2-[18F]-fluoro-L-phenylalanine (18F-FBPA) PET has been employed to estimate 10B accumulation in target tumors and normal tissues if 10B borono-L-phenylalanine (10B-BPA) is used as a boron carrier. The purpose of the current study was to evaluate the total distribution volume (Vt) of 18F-FBPA in normal organs of healthy volunteers by kinetic analysis and to estimate boron concentration in normal organs for the therapeutic dose of 10B-BPA using obtained Vt values.MethodsSix healthy volunteers were injected with 18F-FBPA (3–5 MBq/kg), and 7 PET-CT scans were performed subsequently. 18F-FBPA radioactivity in whole blood and plasma was measured before, and eight times after the injection. PET images were analyzed by PMOD software. Twelve volumetric regions of interest including the brain, heart, right lung, spleen, liver, parotid salivary glands, esophagus, stomach, pancreas, intestines, and bone marrow were drawn manually for each subject and analyzed with the Logan plot and two Ichise multilinear analyses (MA1 and MA2). The better model was defined by several goodness-of-fit parameters and residual distribution. After Vt values had been derived, boron concentration was estimated in ppm for the 10B-BPA-fructose (10B-BPA-fr) dose 30 g 1 and 2 h post-injection using Vt and interpolated plasma activity data.ResultsThe Ichise MA2 model showed the best fit among all models. Akaike Information Criterion (AIC) was the lowest for the Ichise’s MA2 in all regions (mean AIC value − 14.0) comparing to the other models (Logan plot mean AIC 31.4; Ichise MA1 model mean AIC − 4.2). Mean Vt values of the Ichise MA2 model ranged from 0.94 ± 0.14 ml/ml in the pancreas to 0.16 ± 0.02 ml/ml in the right lung. Estimated boron concentration for 10B-BPA-fr had the highest value in the pancreas (14.0 ± 1.9 ppm 1 h after, and 5.7 ± 1.7 ppm 2 h after the 18F-FBPA administration) and the lowest value in the right lung (2.4 ± 0.3 ppm 1 h, and 1.0 ± 0.3 ppm 2 h post-injection).ConclusionThe 10B concentration in normal tissues was best estimated using Vt values of 18F-FBPA with the Ichise multilinear analysis 2 (MA2).Trail registryThe UMIN clinical trial number: UMIN000022850.
Highlights
Boron neutron capture therapy (BNCT) is a rapidly growing area of medicine, at the junction of radionuclide diagnostics, nuclear physics, radiation therapy and, pharmacology
Boron concentration could be estimated at any time point, after the equilibrium state between the influx of the tracer into the tissue compartment and its efflux to the plasma is reached
The volume of distribution represents the ratio of the tracer concentrations in the target tissue (Ct) and plasma (Cp) at equilibrium or steady-state: Vt = Ct/Cp
Summary
Boron neutron capture therapy (BNCT) is a rapidly growing area of medicine, at the junction of radionuclide diagnostics, nuclear physics, radiation therapy and, pharmacology. The ratio of 10B concentration in the tumor and its concentration in normal tissues (T/N ratio) should be more than 3:1, and the 10B concentration in the target should be at least 15 μg/g [7, 8]. Annals of Nuclear Medicine (2020) 34:155–162 is necessary to know the concentration of the 10B in tumor cells and in normal tissues. PET with 4-borono-2-[18F]-fluoro-Lphenylalanine (18F-FBPA) can be used for estimation of 10B concentration in vivo [9] because 18F-FBPA molecule has similar pharmacological behavior in normal tissues to that of 10B-BPA [10, 11]
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