Evaluation of the total distribution volume of (18)F-FBPA in normal tissues of healthy volunteers by non-compartmental kinetic modeling

OBJECTIVE: Boron neutron capture therapy (BNCT) is a noninvasive radiation therapy method for cancer treatment. In BNCT, 4-borono-2-[(18)F]-fluoro-L-phenylalanine ((18)F-FBPA) PET has been employed to estimate (10)B accumulation in target tumors and normal tissues if (10)B borono-L-phenylalanine ((10)B-BPA) is used as a boron carrier. The purpose of the current study was to evaluate the total distribution volume (Vt) of (18)F-FBPA in normal organs of healthy volunteers by kinetic analysis and to estimate boron concentration in normal organs for the therapeutic dose of (10)B-BPA using obtained Vt values. METHODS: Six healthy volunteers were injected with (18)F-FBPA (3–5 MBq/kg), and 7 PET-CT scans were performed subsequently. (18)F-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 (10)B-BPA-fructose ((10)B-BPA-fr) dose 30 g 1 and 2 h post-injection using Vt and interpolated plasma activity data. RESULTS: The 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 (10)B-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 (18)F-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). CONCLUSION: The (10)B concentration in normal tissues was best estimated using Vt values of (18)F-FBPA with the Ichise multilinear analysis 2 (MA2). TRAIL REGISTRY: The UMIN clinical trial number: UMIN000022850. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12149-019-01427-9) contains supplementary material, which is available to authorized users.