Author:
Romanov Victor,Isohashi Kayako,Alobthani Galal,Beshr Rouaa,Horitsugi Genki,Kanai Yasukazu,Naka Sadahiro,Watabe Tadashi,Shimosegawa Eku,Hatazawa Jun
Abstract
Abstract
Objective
Boron 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.
Methods
Six 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.
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 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).
Conclusion
The 10B concentration in normal tissues was best estimated using Vt values of 18F-FBPA with the Ichise multilinear analysis 2 (MA2).
Trail registry
The UMIN clinical trial number: UMIN000022850.
Funder
Ministry of Education, Culture, Sports, Science and Technology
Publisher
Springer Science and Business Media LLC
Subject
Radiology, Nuclear Medicine and imaging,General Medicine
Reference28 articles.
1. Lin YC, Hwang JJ, Wang SJ, Yang BH, Chang CW, Hsiao MC, et al. Macro- and microdistributions of boron drug for boron neutron capture therapy in an animal model. Anticancer Res. 2012;32(7):2657–64.
2. Haritz D, Gabel D, Huiskamp R. Clinical Phase-I study of Na2B12H11SH (BSH) in patients with malignant glioma as precondition for boron neutron capture therapy (BNCT). Int J Radiat Oncol Biol Phys. 1994;28(5):1175–81.
3. Mallesch JL, Moore DE, Allen BJ, McCarthy WH, Jones R, Stening WA. The pharmacokinetics of p-boronophenylalanine fructose in human patients with glioma and metastatic melanoma. Int J Radiat Oncol Biol Phys. 1994;28(5):1183–8.
4. Coderre JA, Chanana AD, Joel DD, Elowitz EH, Micca PL, Nawrocky MM, et al. Biodistribution of boronophenylalanine in patients with glioblastoma multiforme: boron concentration correlates with tumor cellularity. Radiat Res. 1998;149(2):163–70.
5. Kubota R, Yamada S, Ishiwata K, Tada M, Ido T, Kubota K. Cellular accumulation of 18F-labelled boronophenylalanine depending on DNA synthesis and melanin incorporation: a double-tracer microautoradiographic study of B16 melanomas in vivo. Br J Cancer. 1993;67(4):701–5.
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