Boron‐11 NMR of borocaptate: Relaxation and <i>in vivo</i> detection in melanoma‐bearing mice

Bendel, Peter; Frantz, Anatol; Zilberstein, Judith; Kabalka, George W.; Salomon, Yoram

doi:10.1002/mrm.1910390314

Cited by 16 publications

(12 citation statements)

References 17 publications

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“…Although the in vivo T 2 value of 10 B in BSH was not measured yet, one can estimate its expected value, based on experience accumulated from in vivo detection of BSH by 11 B NMR. The fast component of the 11 B transverse relaxation in BSH in a mouse tumor was recently estimated to be of the order of 0.6Ϯ0.2 ms. 6 Figure 3 shows a graph with simulated curves, in which expected T 2 values were calculated for both 11 B and 10 B. The relaxation rates ͑fast and slow components͒ for 11 B were calculated according to Eqs.…”

Section: Discussionmentioning

confidence: 99%

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Optimal detection of the neutron capture therapy agent borocaptate sodium (BSH): A comparison between 1H and 10B NMR

Bendel

Sauerwein

2001

Med. Phys.

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Boron Neutron Capture Therapy (BNCT), an experimental binary cancer treatment modality, requires selective targeting of 10B containing compounds to tumors. One of the compounds under evaluation in an EORTC phase I trial, and used in Japan for patient treatments for many years, is borocaptate sodium (BSH, also known as sulfhydril boron hydride). To optimize the clinical applications, a noninvasive method is needed to monitor the distribution of the boron compound, and NMR may offer such a possibility. A comparison between the relative sensitivities for detecting BSH by 10B or 1H NMR was conducted at two magnetic field strengths: 2 and 4.7 T. At each field strength, similar-sized radio frequency (rf) coils were used for both nuclei. Theoretical predictions for the intrinsic signal to noise (S/N) advantage of 1H over 10B detection vary between a factor of 5.4 and a factor of 28.9, depending on whether the effective resistance is dominated by coil losses or sample losses. Our tests, conducted on relatively small aqueous samples, which loaded the coils less than expected for animal or human subjects, resulted nevertheless in advantage factors close to the lower limit of this range. The measured S/N detection advantage factors for 1H were about 5.2 at 4.7 T, using a dedicated 1H coil, and 7.7 at 2 T, where the measurements were conducted with a double-tuned coil. However, when predicting the expected performance for in vivo MRS or MRI, one should bear in mind that proton detection has to be conducted by spectral-editing pulse sequences with an inherent S/N loss by at least a factor of 2, and that the T1 relaxation time for 10B in BSH is about 30 times shorter than the 1HT1 value. In view of these considerations, direct 10B detection could well be the preferred strategy for MRI/MRS of BSH in vivo.

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Section: Discussionmentioning

confidence: 99%

“…In the case of BSH, 11 B NMR was used in the past for MRS and MRI, in laboratory animals and humans. 5,6 Since the molecules used in clinical practice are Ͼ95% enriched in 10 B, detection through 11 B NMR would be unsuitable. Efforts were therefore directed in the past toward efficient detection of 10 B enriched BSH.…”

Section: Introductionmentioning

confidence: 99%

Optimal detection of the neutron capture therapy agent borocaptate sodium (BSH): A comparison between 1H and 10B NMR

Bendel

Sauerwein

2001

Med. Phys.

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“…The 11 B signal from BSH is considerably broadened in biological environments, such as in serum solutions and in laboratory animals [27][28][29] (Fig. 2).…”

Section: B-relaxation Spectroscopy Imagingmentioning

confidence: 99%

“…2). In 29 a study in which the relaxation rates of the 11 B signal in BSH were measured as a function of concentration in whole horse serum, 29 the results could be fitted using a model in which the BSH molecules are in rapid exchange between a free state, where the molecule is reorienting rapidly (compared with the Larmor frequency), and a bound state (where the re-orientation rate is comparable to, or slower than the Larmor frequency). Under these conditions, the transverse relaxation of 3/2 spins is predicted to follow a bi-exponential decay, where the fast and slow decaying fractions are 60 and 40% of the total signal intensity, respectively, and the relaxation rates for each fraction contain contributions from both the 'free' (BSH in solution) and 'bound' (BSH attached to serum proteins) states.…”

Section: B-relaxation Spectroscopy Imagingmentioning

confidence: 99%

Biomedical applications of10B and11B NMR

Bendel

2005

NMR Biomed.

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This review focuses mainly on the detection and investigation of molecules used for boron neutron capture therapy (BNCT) by 10 B and 11 B NMR. In this binary radiation treatment, boron-containing molecules (also called 'BNCT agents') enriched in the 10 B isotope, are targeted to the tumor, and irradiated with thermal or epithermal neutrons. Capture of these neutrons by 10 B nuclei generates cell-damaging radiation, confined to single cell dimensions. NMR research efforts have primarily been applied in two directions: first, to investigate the metabolism and pharmaco-kinetics of BNCT agents invivo, and second, to use localized NMR spectroscopy and/or MRI for non-invasive mapping of the administered molecules in treated animals or patients. While the first goal can be pursued using 11 B NMR for natural-abundance samples (80% 11 B / 20% 10 B), molecules used in the actual treatment are >95% enriched in 10 B, and must therefore be detected by 10 B NMR. Both 10 B (spin 3) and 11 B (spin 3/2) are quadrupolar nuclei, and their typical relaxation times, in common BNCT agents in biological environments, are rather short. This poses some technical challenges, particularly for MRI, which will be reviewed, along with possible solutions. The first attempts at 11 B NMR and MRI detection of BNCT agents in biological tissue were conducted over a decade ago. Since then, results from 11 B MRI in laboratory animals and in humans have been reported, and 11 B NMR spectroscopy provided interesting and unique information about the metabolism of some BNCT agents in cultured cells. 10 B NMR was applied either 'indirectly' (in double-resonance experiments involving coupled protons), but also by direct 10 B MRI in mice. However, no results involving the NMR detection of 10 B-enriched compounds in treated patients have been reported yet.

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“…The use of nuclear magnetic resonance (NMR) as a potential noninvasive technique for studying the pharmacokinetics of boronated delivery agents in BNCT has previously been proposed. [5][6][7][8] The studies cited have attempted to directly measure the concentrations of boron in biological tissues. Although naturally occurring boron is isotopically composed of approximately 20% B-10 and 80% B-11, the boron that is employed for actual BNCT studies is, typically, >98% isotopically enriched in B-10.…”

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confidence: 99%

Proton nuclear magnetic resonance measurement of p‐boronophenylalanine (BPA): A therapeutic agent for boron neutron capture therapy

et al. 1999

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Noninvasive in vivo quantitation of boron is necessary for obtaining pharmacokinetic data on candidate boronated delivery agents developed for boron neutron capture therapy (BNCT). Such data, in turn, would facilitate the optimization of the temporal sequence of boronated drug infusion and neutron irradiation. Current approaches to obtaining such pharmacokinetic data include: positron emission tomography employing F-18 labeled boronated delivery agents (e.g., pboronophenylalanine), ex vivo neutron activation analysis of blood (and very occasionally tissue) samples, and nuclear magnetic resonance (NMR) techniques. In general, NMR approaches have been hindered by very poor signal to noise achieved due to the large quadrupole moments of B-10 and B-11 and (in the case of B-10) very low gyromagnetic ratio, combined with low physiological concentrations of these isotopes under clinical conditions. This preliminary study examines the feasibility of proton NMR spectroscopy for such applications. We have utilized proton NMR spectroscopy to investigate the detectability of p-boronophenylalanine fructose (BPA-f) at typical physiological concentrations encountered in BNCT. BPA-f is one of the two boron delivery agents currently undergoing clinical phase-I/II trials in the U.S., Japan, and Europe. This study includes high-resolution 1 H spectroscopic characterization of BPA-f to identify useful spectral features for purposes of detection and quantification. The study examines potential interferences, demonstrates a linear NMR signal response with concentration, and presents BPA NMR spectra in ex vivo blood samples and in vivo brain tissues.

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Boron‐11 NMR of borocaptate: Relaxation and in vivo detection in melanoma‐bearing mice

Cited by 16 publications

References 17 publications

Optimal detection of the neutron capture therapy agent borocaptate sodium (BSH): A comparison between 1H and 10B NMR

Optimal detection of the neutron capture therapy agent borocaptate sodium (BSH): A comparison between 1H and 10B NMR

Biomedical applications of10B and11B NMR

Proton nuclear magnetic resonance measurement of p‐boronophenylalanine (BPA): A therapeutic agent for boron neutron capture therapy

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