T2 corrected quantification method of l-p-boronophenylalanine using proton magnetic resonance spectroscopy for boron neutron capture therapy

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Abstract

In the present study, we aimed to evaluate a T2 corrected quantification method of l-p-boronophenylalanine (BPA) concentration using proton magnetic resonance spectroscopy (MRS). We used five phantoms containing BPA (1.5, 3.0, 5.0, 7.5, and 10 mmol/kg=15, 30, 50, 75, and 100 μg10B/g), N-acetyl-aspartic acid (NAA: 3.0 mmol/kg), creatine (Cr: 5.0 mmol/kg), and choline (Cho: 3.0 mmol/kg). The signal intensities of BPA and internal water were corrected by T2 relaxation time. The absolute concentrations of BPA were calculated by proton MRS using an internal water signal as a standard. The major BPA peaks were detected between 7.1 and 7.6 ppm. Mean T2 relaxation time was 314.3±10.8 ms in BPA, 885.1±39.7 ms in internal water. The calculated BPA concentrations were almost same as the actual concentration of BPA and the correlation coefficient was 0.99. Our BPA quantification method was very simple and non-invasive, also it had high accuracy. Therefore, our results indicate that proton MRS can be potentially useful technique for in vivo BPA quantification in boron neutron capture therapy (BNCT).

Introduction

Boron neutron capture therapy (BNCT) is a radiation therapy using α-ray and Li particles. The charged particles attack only tumor cells containing boron-10 (10B). Therefore, BNCT is a tumor-selective radiation therapy at the cellular level (Barth et al., 2005; Yamamoto et al., 2008). Quantitative information regarding local 10B concentrations is crucial to determining the optimal timing of the neutron irradiation and to calculating the radiation dose for the treatment planning. As a 10B carrier, l-p-boronophenylalanine (BPA) is widely used in clinical BNCT for malignant brain tumor and skin melanoma, as well as head and neck cancer. In the clinical case, BPA tumor uptake and systemic distribution were determined by the pharmacokinetic analysis of discontinuous venous blood samples. The concentrations of 10B in tumor-cells were estimated using empirical data models. Empirical data models depend on tumor-to-blood, tumor-to-brain and brain-to-blood 10B concentration ratios. One of the problems is that the uptake and distribution of 10B varies among patients and that large uncertainties exist regarding the tumor-to-blood 10B concentration ratio. Recently, positron emission tomography (PET) has been used for determining 10B uptake and distribution in pretreatment rehearsal studies (Nichols et al., 2002). In addition, PET examination with 18F-labeled BPA (18F-BPA) can demonstrate 10B mapping in the brain. However, this rehearsal infusion is different from the BPA administration during actual treatment because PET examination requires only a low dose of 18F-BPA. In addition, the synthesis of 18F-BPA is very complicated and limited. We have only two institutions that can synthesize 18F-BPA in Japan. Therefore, a new method enabling us to directly determine BPA concentration in vivo will improve the accuracy of BNCT.

Proton magnetic resonance spectroscopy (MRS) is a noninvasive and in vivo biochemical assay allowing us to determine and quantify brain metabolites (Isobe et al., 2002). According to previous studies (Bendel et al., 2005; Heikkinen et al., 2003; Zuo et al., 1999), the resonance signals of BPA can be detected using proton MRS. In addition, it was also possible to quantify BPA concentrations. However, in these studies, the correction of relaxation time and the study of the quantification method applying to clinical cases utilizing BNCT were insufficient. For proper quantification, T2 relaxation time is need in adjustment, because T2 affects the resonance signals, and T2 is changed by various factors.

In the present study, we aimed to evaluate a T2 corrected quantification method for BPA concentrations using proton MRS.

Section snippets

Phantoms

We used five phantoms containing BPA (1.5, 3.0, 5.0, 7.5, and 10 mmol/kg=15, 30, 50, 75, and 100 μg10B/g), N-acetyl-aspartic acid (NAA: 3.0 mmol/kg), creatine (Cr: 5.0 mmol/kg), and choline (Cho: 3.0 mmol/kg). The inside of the phantom was filled with saline. Fig. 1 shows the BPA phantoms that we made. The phantom consisted of a cylindrical acryl tray and a glass chamber.

Proton MRS

Proton MRS was performed using a clinical 1.5 T superconducting magnetic resonance (MR) whole-body system (Gyroscan ACS-NT Intera;

Results

We have identified several characteristic resonances. The chemical shift of BPA in the phantom was corrected using the chemical shift of the Cho peak (3.22 ppm) as a standard. The major BPA peaks were detected between 7.1 and 7.6 ppm.

Fig. 3 shows the spectrum of BPA between 6 and 8 ppm. We considered that some big BPA peaks were well-suited to quantification of BPA, while others were essentially obscured by resonance signals from brain metabolites.

We measured the T1 and T2 relaxation times of BPA

Conclusions

We were able to quantify the concentrations of BPA in a phantom using a 1.5 T clinical MR machine. Our results indicate that proton MRS is a potentially useful technique for in vivo BPA quantification in BNCT.

Acknowledgment

This study was supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture, Japan (20390379).

References (10)

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