In Vivo detection of a boron‐neutron‐capture agent in melanoma by proton observed 1H ‐ 10B double resonance

Bendel, Peter; Zilberstein, Judith; Salomon, Yoram

doi:10.1002/mrm.1910320204

Cited by 31 publications

(22 citation statements)

References 16 publications

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“…A simple version of this approach is the subtraction of a spin-echo signal which is modulated by the 10 B-1 H coupling (achieved by applying simultaneous pulses to the boron and proton channels) from a non-modulated echo. Such an experiment was applied in-vivo to the detection of BSSB (a dimer of BSH created by formation of an S-S bond between two BSH molecules) from a mouse melanoma tumor, 42 and subsequently analyzed theoretically in more detail, ignoring relaxation. 43 However, since 1/T 1 of the boron spins can be short compared with the scalar coupling constant (particularly in-vivo), the 10 B spinlattice relaxation has a significant influence on the 1 H echo evolution, an effect known as scalar relaxation.…”

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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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Biomedical applications of10B and11B NMR

Bendel

2005

NMR Biomed.

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“…Mice (n ϭ 3) with tumors grown to about 1-2 cm in size were used for MRI experiments and 10 B relaxation time measurements (7). A solution (180 l) containing 0.11 M of 10 B-enriched (Ͼ95%) BSH (Boron Biologicals, Raleigh, NC) in PBS was injected into the mice tail veins.…”

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confidence: 99%

In vivo imaging of the neutron capture therapy agent BSH in mice using ¹⁰B MRI

Bendel

Koudinova

Salomon

2001

Magnetic Resonance in Med

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Boron neutron capture therapy (BNCT) is an experimental cancer treatment modality requiring the targeting of 10 B-enriched compounds to the tumor, which is then irradiated by low-energy neutrons. One of the boron-containing compounds used for this purpose is the mercaptoborane Na 2 B 12 H 11 SH (BSH). The first in vivo MR images of 10 B-enriched BSH are presented here. BSH, injected into the tail vein of mice with implanted M2R melanoma xenografts, was imaged using 3D gradient echo 10 B MRI. 10 B NMR spectroscopy, localized mainly to the tumor by virtue of the use of a small surface coil, was applied to measure the T 1 (2.9 ؎ 0. Boron neutron capture therapy (BNCT) is based on the high cross section of 10 B for capturing thermal neutrons (1,2). This nuclear reaction yields alpha particles and recoiling lithium nuclei, both with high linear energy transfer (LET) and relatively short spatial range (ϳ10 m). Therefore, the combined targeting of neutron irradiation and boron accumulation can lead to selective damaging of tumor cells. Borocaptate sodium, Na 2 B 12 H 11 SH (BSH) was used as BNCT agent in Japanese patients since 1968 (3) and is now under evaluation in a European Phase I clinical trial (4).The ability for noninvasive imaging of the administered drug is a highly desirable goal for both the research of BNCT and for its clinical implementation. So far, the in vivo MR imaging of BSH was demonstrated only for the natural abundance compound (5), using 11 B detection ( 11 B has 80% natural abundance). This approach is obviously not suitable for clinical applications, where the boronated molecules are enriched in 10 B to over 95%. It was always assumed that direct 10 B detection would not be sensitive enough for MRI of BNCT agents, due to the low gyromagnetic ratio of 10 B, and therefore considerable efforts were devoted to the development and implementation of indirect detection methods. In BSH, 11 out of the 12 boron nuclei are coupled to protons (J ϭ 43 Hz) and several reports exploiting this fact for 10 B-edited, proton detection of BSH were published (6 -9). We decided, nevertheless, to explore the possibility for direct 10 B MRI of BSH, following measurements indicating that indirect 1 H detection may not be as advantageous as previously assumed (10). MATERIALS AND METHODSMouse M2R melanoma cells, routinely maintained as monolayers, were scraped, suspended in saline at 1 ϫ 10 6 cells / 0.25 ml, and injected subcutaneously into the rear thigh of CD1 nude mice. Mice (n ϭ 3) with tumors grown to about 1-2 cm in size were used for MRI experiments and 10 B relaxation time measurements (7). A solution (180 l) containing 0.11 M of 10 B-enriched (Ͼ95%) BSH (Boron Biologicals, Raleigh, NC) in PBS was injected into the mice tail veins. During the injection and the subsequent NMR experiments, the mice were anesthetized with Isoflurane (Medeva, Bethlehem, PA) in 70% N 2 O/30% O 2 . NMR experiments were conducted on a spectrometer with a 4.7T horizontal 30 cm bore magnet (Biospec, Bruker, Ettlingen, Germany). For MRI, ...

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“…B magnetic resonance imaging (MRI) was proposed as a non-invasive method for the in vivo assessment of BNCT agents, but its practical utilization still remains to be proven. 50,51 The other recently developed approach is 19 F MRI of fluorine-containing BPA derivatives. 52 …”

Section: Study Of Biodistribution and Pharmacokineticsmentioning

confidence: 99%