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

Abstract

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 goodnessof-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.

Physical bases of Boron Neutron Capture Therapy, Dosimetry, and Its Mechanisms of Action - Critical Overview of the Literature

“…Additionally, it should also be considered that the uptake of the boroncarrying molecules in target cells is heterogeneous. It depends on factors like tumor cellularity (i.e., the number of tumor cells arranged in clusters) [61], cell cycle phase, and others) [62]. It is one of the crucial factors, often marked as a drawback in BNCT, because it causes ambiguity in the calculated dose distributions.…”

“…Positron emission tomography has many abilities, such as (I) quantifying biochemical processes, (II) reconstructing the distribution of a boron carrier (this information can be later used in treatment planning), (III) locating and determining the extent of metastasis in the body, (IV) predicting the optimal time of neutron exposure to BNCT, (V) controlling the therapeutic effects, and (VI) assessing whether the patient is suitable for BNCT. The suitability of positron emission tomography for the establishment of boron concentration in healthy tissues and tumors and the needs of treatment planning have been examined in many studies [62,66,67]. However, PET imaging with the current technology can mainly measure the boron distribution before the treatment.…”

Clinical Viability of Boron Neutron Capture Therapy for Personalized Radiation Treatment

“…Furthermore, it should also be noted that the uptake of boron-carrying molecules in target cells is heterogeneous. It depends on factors, such as tumor cellularity (that is, the number of tumor cells arranged in clusters), cell cycle phase, and others [ 77 , 78 ].…”

Enzymatic synthesis of fluorinated compounds

“…This ( 18 F-DOPA) PET could be applied to assess the volume of remaining gliomas in the patient, Parkinson's syndrome, and focal hyperinsulinemia in infants, which was a perfect complement to the traditional detection technology. Except that, other types of fluorinated compounds were also used as PET tracers for cancer and tumor detection, such as 18 F-PSMA-1007 (Dietlein et al 2020 ), l -2- 18 F-FAMP, d -2/3/4- 18 F-FAMP and l -3- 18 F-FAMT (Hanaoka et al 2019 ; Mahendra et al 2020 ; Shimizu et al 2019 ), ( 18 F-FBPA) (Romanov et al 2020 ), 18 F-fluoro-ethyl- l -tyrosine ( 18 F-FET) (Fuenfgeld et al 2020 ; Marner et al 2019 ), 6- 18 F-fluoro-meta-tyrosine ( 18 F-FMT) (Badin et al 2019 ; Kojima et al 2019 ; Miyamoto et al 2020 ), N -[ 18 F]-fluoropropylJDTic (Schmitt et al 2017 ), 2-(3-(1-carboxy-5-[(6- 18 F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid ( 18 F-DCFPyL) (Jansen et al 2019 ; Rousseau et al 2019 ; Rowe et al 2020a , 2020b ), 5- 18 F-fluoro- l -amino suberate ( 18 F-FASu) (Alluri et al 2020 ; Colovic et al 2019 ), 4-borono-2- 18 F-fluoro- l -phenylalanine fluorine substituted 3-azabicyclo hexane (Chen et al 2019b ), and [ 18 F]FDA-PEG-biotin/tetrazine (Lowe et al 2018 ). Therefore, PET tracers based on new fluorinated compounds will play an increasing role in the field of visual detection technology.…”