Dose Rate Effect on Cell Survival in BNCT.

The output constancy of the accelerator used for boron neutron capture therapy (BNCT) is essential to ensuring anti-tumor efficacy and safety. BNCT as currently practiced requires a wide variety of beam quality assessments to ensure that RBE dose errors are maintained within 5%. However, the necessity of maintaining a constant beam dose rate has not been fully discussed. We therefore clarified the effect of different physical dose rates of the accelerator BNCT on biological effects. SAS and A172 cells exposed to 10B-boronophenylalanine were irradiated using a neutron beam (normal operating current, 100 µA) at the Aomori Quantum Science Center. Thermal neutron flux was attenuated to 50.0 ± 0.96% under 50 µA irradiation compared to that under 100 µA irradiation. Cells were given physical doses of 1.67 and 3.36 Gy at 30 and 60 mC, respectively, and survival was significantly increased after 50 µA irradiation for both cell types (p = 0.0052 for SAS; p = 0.046 for A172, for 60 mC). Differences in accelerator BNCT beam dose rates have non-negligible effects on biological effects. Dose rate fluctuations and differences should not be easily permitted to obtain consistent biological effects.

Rational Design, Multistep Synthesis and in Vitro Evaluation of Poly(glycerol) Functionalized Nanodiamond Conjugated with Boron-10 Cluster and Active Targeting Moiety for Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT), advanced cancer treatment utilizing nuclear fission of 10 B atom in cancer cells, is attracting increasing attention. As 10 B delivery agent, sodium borocaptate (10 BSH, 10 B12 H11 SH ⋅ 2Na), has been used in clinical studies along with L-boronophenylalanine. Recently, this boron cluster has been conjugated with lipids, polymers or nanoparticles to increase selectivity to and retentivity in tumor. In this work, anticancer nanoformulations for BNCT are designed, consisting of poly(glycerol) functionalized detonation nanodiamonds (DND-PG) as a hydrophilic nanocarrier, the boron cluster moiety (10 B12 H11 2- ) as a dense boron-10 source, and phenylboronic acid or RGD peptide as an active targeting moiety. Some hydroxy groups in PG were oxidized to carboxy groups (DND-PG-COOH) to conjugate the active targeting moiety. Some hydroxy groups in DND-PG-COOH were then transformed to azide to conjugate 10 B12 H11 2- through click chemistry. The nanodrugs were evaluated in vitro using B16 murine melanoma cells in terms of cell viability, BNCT efficacy and cellular uptake. As a result, the 10 B12 H11 2- moiety is found to facilitate cellular uptake probably due to its negative charge. Upon thermal neutron irradiation, the nanodrugs with 10 B12 H11 2- moiety exhibited good anticancer efficacies with slight differences with and without targeting moiety.

Advances in Boron Neutron Capture Therapy (BNCT) for Recurrent Intracranial Meningioma.

Meningiomas are the most frequently diagnosed primary intracranial tumors in adults. Surgical resection is preferred if the meningioma is accessible; for those that are not suitable for surgical resection, radiotherapy should be considered to improve local tumor control. However, recurrent meningiomas are challenging to treat, as the recurrent tumor might be located in the previously irradiated area. Boron Neutron Capture Therapy (BNCT) is a highly selective radiotherapy modality in which the cytotoxic effect focuses mainly on cells with increased uptake of boron-containing drugs. In this article, we describe four patients with recurrent meningiomas treated with BNCT in Taiwan. The mean boron-containing drug tumor-to-normal tissue uptake ratio was 4.125, and the tumor mean dose was 29.414 GyE, received via BNCT. The treatment response showed two stable diseases, one partial response, and one complete response. We also introduce and support the effectiveness and safety of BNCT as an alternative salvage treatment for recurrent meningiomas.

Synthesis, equilibrium, and biological study of a C-7 glucose boronic acid derivative as a potential candidate for boron neutron capture therapy.

The synthesis of d-glucoheptose derivative containing a boronic moiety is described herein. Starting from benzyl 6,7-dideoxy-2,3,4-tri-O-benzyl-ß-d-gluco-ept-6-enopyranoside, the introduction of the boronic acid was performed through a metathesis reaction by using MIDA vinyl boronic acid and the 2nd generation Grubbs catalyst. Hydrogenation led to the final product in only two reaction steps. This new sugar-containing boronic acid in the skeleton could mimic carbohydrate behavior and follow the glucose uptake in living cells. The in vitro toxicity tests performed in fibroblasts and glioma tumor cell lines showed minimal toxicity. Boron uptake measured using ICP-MS was minimal in fibroblasts, while in glioma cells showed a value of 6 ng of total boron accumulation per mg of cells, implying that compound 1a is able to accumulate selectively in the tumor tissues compared to normal.

Boron phenyl alanine targeted chitosan-PNIPAAm core-shell thermo-responsive nanoparticles: boosting drug delivery to glioblastoma in BNCT.

Boron neutron capture therapy (BNCT) is one of the best treatment modalities for glioblastoma multiform that could selectively kill the tumor cells. To be successful in BNCT, it is crucial to have enough 10B in the tumor. l-boron phenylalanine (l-BPA) targeted thermo-responsive core-shell nanoparticles (NPs) of chitosan-poly(N-isopropylacrylamide) (PNIPAAm) were our idea for endocytosis via sialic acid receptors, and selective delivery of 10B to glial cells. Methotrexate (MTX) was chosen as a model drug for evaluating the efficacy of NPs in tumor cells, and BPA was selected for BNCT purposes. The polymeric conjugates were synthesized and the chemical structures were approved by spectroscopic methods (FTIR, 1H NMR, and 11B NMR). Cargos were loaded efficiently (>95%) in the prepared NPs, and the release profile of MTX and BPA was studied around the lower critical solution temperature (LCST; about 39 °C). The loaded drugs were released quantitatively at the LCST, while almost no drug was released at 37 °C. The prepared NPs did not show considerable hemolysis ratio (<2%) and were still safe when loaded BPA, on U87MG cells. The MTX loaded NPs showed lower IC50 (30.78 µg/mL) than the free MTX (37.03 µg/mL) in MTT assay, and targeted NPs had the lowest IC50s in U87MG cell lines (27.35 µg/mL). Targeted BPA@CSSU-PNI NPs were uptaken better than the non-targeted ones by U87MG cells, and CR-39 assay showed the boron content efficiency for further applications in BNCT. This study's results introduce novel targeted thermo-responsive NPs for treating glioblastoma using BNCT.

Development of MRI-Detectable Boron-Containing Gold Nanoparticle-Encapsulated Biodegradable Polymeric Matrix for Boron Neutron Capture Therapy (BNCT).

This study aimed to develop a novel magnetic resonance imaging (MRI)-detectable boron (B)-containing nanoassemblies and evaluate their potential for boron neutron capture therapy (BNCT). Starting from the citrate-coated gold nanoparticles (AuNPs) (23.9 ± 10.2 nm), the diameter of poly (D, L-lactide-co-glycolide) AuNPs (PLGA-AuNPs) increased approximately 110 nm after the encapsulation of the PLGA polymer. Among various B drugs, the self-produced B cages had the highest loading efficiency. The average diameter of gadolinium (Gd)- and B-loaded NPs (PLGA-Gd/B-AuNPs) was 160.6 ± 50.6 nm with a B encapsulation efficiency of 28.7 ± 2.3%. In vitro MR images showed that the signal intensity of PLGA-Gd/B-AuNPs in T1-weighted images was proportional to its Gd concentration, and there exists a significantly positive relationship between Gd and B concentrations (R2 = 0.74, p < 0.005). The hyperintensity of either 250 ± 50 mm3 (larger) or 100 ± 50 mm3 (smaller) N87 xenograft was clearly visualized at 1 h after intravenous injection of PLGA-Gd/B-AuNPs. However, PLGA-Gd/B-AuNPs stayed at the periphery of the larger xenograft while located near the center of the smaller one. The tumor-to-muscle ratios of B content, determined by inductively coupled plasma mass spectrometry, in smaller- and larger-sized tumors were 4.17 ± 1.42 and 1.99 ± 0.55, respectively. In summary, we successfully developed theranostic B- and Gd-containing AuNPs for BNCT in this study.

Synthesis, Molecular Docking, and In Vitro Boron Neutron Capture Therapy Assay of Carboranyl Sinomenine.

In comparison with pristine sinomenine and carborane precursors, the calculations of molecular docking with matrix metalloproteinases (MMPs) and methylcarboranyl-n-butyl sinomenine showed improved interactions. Accordingly, methylcarboranyl-n-butyl sinomenine shows a high potential in the treatment of rheumatoid arthritis (RA) in the presence of slow neutrons. The reaction of potassium salt of sinomenie, which is generated from the deprotonation of sinomenine (1) using potassium carbonate in a solvent of N,N-dimethyl formamide, with 4-methylcarboranyl-n-butyl iodide, (2) forms methylcarboranyl-n-butyl sinomenine (3) in 54.3% yield as a new product. This new compound was characterized by 1H, 13C, and 11B NMR spectroscopy, FT-IR spectroscopy, and elemental analyses to confirm its molecular composition. In addition to molecular docking interactions with MMPs, the in vitro killing effects of 3, along with its toxicity measurements, exhibited its potential to be the new drug delivery agent for boron neutron capture synovectomy (BNCS) and boron neutron capture therapy (BNCT) for the treatment of rheumatoid arthritis (RA) and cancers in the presence of slow neutrons, respectively.

Synthesis and Initial Biological Evaluation of Boron-Containing Prostate-Specific Membrane Antigen Ligands for Treatment of Prostate Cancer Using Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is a therapeutic modality which has been used for the treatment of cancers, including brain and head and neck tumors. For effective treatment via BNCT, efficient and selective delivery of a high boron dose to cancer cells is needed. Prostate-specific membrane antigen (PSMA) is a target for prostate cancer imaging and drug delivery. In this study, we conjugated boronic acid or carborane functional groups to a well-established PSMA inhibitor scaffold to deliver boron to prostate cancer cells and prostate tumor xenograft models. Eight boron-containing PSMA inhibitors were synthesized. All of these compounds showed a strong binding affinity to PSMA in a competition radioligand binding assay (IC50 from 555.7 to 20.3 nM). Three selected compounds 1a, 1d, and 1f were administered to mice, and their in vivo blocking of 68Ga-PSMA-11 uptake was demonstrated through a positron emission tomography (PET) imaging and biodistribution experiment. Biodistribution analysis demonstrated boron uptake of 4-7 µg/g in 22Rv1 prostate xenograft tumors and similar tumor/muscle ratios compared to the ratio for the most commonly used BNCT compound, 4-borono-l-phenylalanine (BPA). Taken together, these data suggest a potential role for PSMA targeted BNCT agents in prostate cancer therapy following suitable optimization.

Electroporation optimizes the uptake of boron-10 by tumor for boron neutron capture therapy (BNCT) mediated by GB-10: a boron biodistribution study in the hamster cheek pouch oral cancer model.

Boron neutron capture therapy (BNCT) is a promising cancer binary therapy modality that utilizes the nuclear capture reaction of thermal neutrons by boron-10 resulting in a localized release of high- and low-linear energy transfer (LET) radiation. Electrochemotherapy (ECT) is based on electroporation (EP) that induces opening of pores in cell membranes, allowing the entry of compounds. Because EP is applied locally to a tumor, the compound is incorporated preferentially by tumor cells. Based on the knowledge that the therapeutic success of BNCT depends centrally on the boron content in tumor and normal tissues and that EP has proven to be an excellent facilitator of tumor biodistribution of an anti-tumor agent, the aim of this study was to evaluate if EP can optimize the delivery of boronated compounds. We performed biodistribution studies and qualitative microdistribution analyses of boron employing the boron compound sodium decahydrodecaborate (GB-10) + EP in the hamster cheek pouch oral cancer model. Syrian hamsters with chemically induced exophytic squamous cell carcinomas were used. A typical EP treatment was applied to each tumor, varying the moment of application with respect to the administration of GB-10 (early or late). The results of this study showed a significant increase in the absolute and relative tumor boron concentration and optimization of the qualitative microdistribution of boron by the use of early EP + GB-10 versus GB-10 without EP. This strategy could be a tool to improve the therapeutic efficacy of BNCT/GB-10 in vivo.

Neutron Autoradiography Combined With UV-C Sensitization: Toward the Intracellular Localization of Boron.

Our group has reported the imprint formation of biological material on polycarbonate nuclear track detectors by UV-C exposure, which is used as an approach to simultaneously visualize cell imprints and nuclear tracks coming from the boron neutron capture reaction. Considering that the cell nucleus has a higher UV-C absorption than the cytoplasm and that hematoxylin preferentially stains the nucleus, we proposed to enhance the contrast between these two main cell structures by hematoxylin staining before UV-C sensitization. In this study, several experiments were performed in order to optimize UV-C exposure parameters and chemical etching conditions for cell imprint formation using the SK-BR-3 breast cancer cell line. The proposed method improves significantly the resolution of the cell imprints. It allows clear differentiation of the nucleus from the rest of the cell, together with nuclear tracks pits. Moreover, it reduces considerably the UV-C exposure time, an important experimental issue. The proposed methodology can be applied to study the boron distribution independently from the chosen cell line and/or boron compounds.

Boron-incorporating hemagglutinating virus of Japan envelope (HVJ-E) nanomaterial in boron neutron capture therapy.

Combining immunotherapeutic and radiotherapeutic technique has recently attracted much attention for advancing cancer treatment. If boron-incorporated hemagglutinating virus of Japan-envelope (HVJ-E) having high membrane fusion ability can be used as a boron delivery agent in boron neutron capture therapy (BNCT), a radical synergistic improvement of boron accumulation efficiency into tumor cells and antitumor immunity may be induced. In this study, we aimed to develop novel boron-containing biocompatible polymers modified onto HVJ-E surfaces. The copolymer consisting of 2-methacryloyloxyethyl phosphorylcholine (MPC) and methacrylamide benzoxaborole (MAAmBO), poly[MPC-co-MAAmBO], was successfully synthesized by using a simple free radical polymerization. The molecular structures and molecular weight of the poly[MPC-co-MAAmBO] copolymer were characterized by nuclear magnetic resonance and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, respectively. The poly[MPC-co-MAAmBO] was coated onto the HVJ-E surface via the chemical bonding between the MAAmBO moiety and the sugar moiety of HVJ-E. DLS, AFM, UV-Vis, and fluorescence measurements clarified that the size of the poly[MPC-co-MAAmBO]-coated HVJ-E, HVJ-E/p[MPC-MAAmBO], to be about 130 ~ 150 nm in diameter, and that the polymer having 9.82 × 106 ~ 7 boron atoms was steadily coated on a single HVJ-E particle. Moreover, cellular uptake of poly[MPC-co-MAAmBO] could be demonstrated without cytotoxicity, and the hemolysis could be successfully suppressed by 20%. These results indicate that the HVJ-E/p[MPC-MAAmBO] may be used as boron nanocarriers in a combination of immunotherapy with BNCT.

Feasibility study on the use of 230 MeV proton cyclotron in proton therapy centers as a spallation neutron source for BNCT.

AIM: The feasibility of using 230 MeV proton cyclotrons in proton therapy centers as a spallation neutron source for Boron Neutron Capture Therapy (BNCT) was investigated. BACKGROUND: BNCT is based on the neutron irradiation of a 10B-containing compound located selectively in tumor cells. Among various types of neutron generators, the spallation neutron source is a unique way to generate high-energy and high-flux neutrons. MATERIALS AND METHODS: Neutron beam was generated by a proton accelerator via spallation reactions and then the produced neutron beam was shaped to be appropriate for BNCT. The proposed Beam Shaping Assembly (BSA) consists of different moderators, a reflector, a collimator, as well as thermal and gamma filters. In addition, the simulated Snyder head phantom was utilized to evaluate the dose distribution in tumor and normal tissue due to the irradiation by the designed beam. MCNPX2.6 Monte Carlo code was used to optimize BSA as well as evaluate dose evaluation. RESULTS: A BSA was designed. With the BSA configuration and a beam current of 104 nA, epithermal neutron flux of 3.94 × 106 [n/cm2] can be achieved, which is very low. Provided that we use the beam current of 5.75 µA, epithermal neutron flux of 2.18 × 108 [n/cm2] can be obtained and the maximum dose of 38.2 Gy-eq can be delivered to tumor tissue at 1.4 cm from the phantom surface. CONCLUSIONS: Results for 230 MeV protons show that with proposed BSA, proton beam current about 5.75 µA is required for this purpose.

Metallacarboranes on the Road to Anticancer Therapies: Cellular Uptake, DNA Interaction, and Biological Evaluation of Cobaltabisdicarbollide [COSAN].

After uptake by U87 MG and A375 cancer cells, cobaltabisdicarbollide [COSAN]- distributes between membrane and nucleus and presents no relevant cytotoxicity against both cell lines even for long incubation times. The cytotoxicity of Na[COSAN] was also tested towards one normal cell line, the V79 fibroblasts, in order to ascertain the noncytotoxic profile of the compound. As the cell's nucleus contains DNA, the interaction between [COSAN]- and double-stranded calf thymus DNA (CT-dsDNA) has been investigated. There is a strong interaction between both molecules forming a nanohybrid CT-dsDNA-[COSAN] biomaterial, which was fully characterized. Moreover, Na[COSAN] shows characteristic redox peaks ascribed to the oxidation/reduction of Co3+/2+ at a formal potential of -1.444 V and it can be accumulated at a surface-immobilized DNA layer of glassy carbon electrodes. The equilibrium surface-binding constants (Kox /Kred ), which confirm that [COSAN]- interacts with DNA by an intercalative or electrostatic mode, depending on the ionic strength of the solution, were estimated. In addition, high binding affinity of Na[COSAN] to proteins was observed by 11 B{1 H} NMR and confirmed in vivo. Finally, biodistribution studies of [COSAN]- in normal mice were run. After administration, Na[COSAN] was distributed into many organs but mainly accumulated in the reticuloendothelial system (RES), including liver and spleen. After 1 h, the formation of aggregates by plasma protein interaction plays a role in the biodistribution profile; the aggregates accumulate mostly in the lungs. Na[COSAN], which displays low toxicity and high uptake by relevant cancer cells accumulating boron within the nucleus, could act as a suitable compound for further developments as boron neutron capture therapy (BNCT) agents.

Design and synthesis of boron containing monosaccharides by the hydroboration of d-glucal for use in boron neutron capture therapy (BNCT).

Boron neutron capture therapy (BNCT) is one of the radiotherapies that involves the use of boron-containing compounds for the treatment of cancer. Boron-10 (10B) containing compounds that can accumulate in tumor tissue are expected to be suitable agents for BNCT. We report herein on the design and synthesis of some new BNCT agents based on a d-glucose scaffold, since glycoconjugation has been recognized as a useful strategy for the specific targeting of tumors. To introduce a boryl group into a d-glucose scaffold, we focused on the hydroboration of d-glucal derivatives, which have a double bond between the C1 and C2 positions. It was hypothesized that a C-B bond could be introduced at the C2 position of d-glucose by the hydroboration of d-glucal derivatives and that the products could be stabilized by conversion to the corresponding boronic acid ester. To test this hypothesis, we prepared some 2-boryl-1,2-dideoxy-d-glucose derivatives as boron carriers and evaluated their cytotoxicity and cellular uptake activity to cancer cells, especially under hypoxic conditions.

Radiation absorbed dose estimates for 18F-BPA PET.

Background Boron neutron capture therapy (BNCT) is a molecular radiation therapy approach based on the 10B (n, α) 7Li nuclear reaction in cancer cells. In BNCT, delivery of 10B in the form of 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is important. The PET tracer 4-borono-2-18F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. Purpose To determine the biodistribution and dosimetric parameters in 18F-BPA PET/CT studies. Material and Methods Human biokinetic data were obtained during clinical 18F-BPA PET studies between February and June 2015 at one institution. Nine consecutive patients were studied prospectively. The internal radiation dose was calculated on the basis of radioactivity data from blood, urine, and normal tissue of the heart, liver, spleen, kidney, and other parts of the body at each time point using OLINDA/EXM1.1 program. We compared our calculations with published 18F-FDG data. Results Adult patients (3 men, 3 women; age range, 28-68 years) had significantly smaller absorbed doses than pediatric patients (3 patients; age range, 5-12 years) ( P = 0.003). The mean effective dose was 57% lower in adult patients compared with pediatric patients. Mean effective doses for 18F-BPA were 25% lower than those for 18F-FDG presented in International Commission of Radiation Protection (ICRP) publication 106. Conclusion We found significant differences in organ absorbed doses for 18F-BPA against those for 18F-FDG presented in ICRP publication 106. Mean effective doses for 18F-BPA were smaller than those for 18F-FDG in the publication by 0.5-38% (mean difference, 25%).

Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new "B2" configuration of the RA-6 nuclear reactor.

Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new "B2" configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in "B1" experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94-96%) than in control (16%) and BO groups (9-38%), and did not differ significantly from the "B1" results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control.

Evaluation of radioactivity in the bodies of mice induced by neutron exposure from an epi-thermal neutron source of an accelerator-based boron neutron capture therapy system.

This study aimed to evaluate the residual radioactivity in mice induced by neutron irradiation with an accelerator-based boron neutron capture therapy (BNCT) system using a solid Li target. The radionuclides and their activities were evaluated using a high-purity germanium (HP-Ge) detector. The saturated radioactivity of the irradiated mouse was estimated to assess the radiation protection needs for using the accelerator-based BNCT system. 24Na, 38Cl, 80mBr, 82Br, 56Mn, and 42K were identified, and their saturated radioactivities were (1.4 ± 0.1) × 102, (2.2 ± 0.1) × 101, (3.4 ± 0.4) × 102, 2.8 ± 0.1, 8.0 ± 0.1, and (3.8 ± 0.1) × 101 Bq/g/mA, respectively. The 24Na activation rate at a given neutron fluence was found to be consistent with the value reported from nuclear-reactor-based BNCT experiments. The induced activity of each nuclide can be estimated by entering the saturated activity of each nuclide, sample mass, irradiation time, and proton current into the derived activation equation in our accelerator-based BNCT system.

Antitumor effect of boron nitride nanotubes in combination with thermal neutron irradiation on BNCT.

The first BNCT antitumor effects of BNNTs toward B16 melanoma cells were demonstrated. The use of DSPE-PEG2000 was effective for preparation of the BNNT-suspended aqueous solution. BNNT-DSPE-PEG2000 accumulated in B16 melanoma cells approximately three times higher than BSH and the higher BNCT antitumor effect was observed in the cells treated with BNNT-DSPE-PEG2000 compared to those treated with BSH, indicating that BNNT-DSPE-PEG2000 would be a possible candidate as a boron delivery vehicle for BNCT.

A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment.

This study aims at developing an innovative theranostic approach for lung tumor and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It relies on to the use of low density lipoproteins (LDL) as carriers able to maximize the selective uptake of boron atoms in tumor cells and, at the same time, to quantify the in vivo boron distribution by magnetic resonance imaging (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung metastases were generated by intravenous injection of a Her2+ breast cancer cell line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary tumor model. After neutron irradiation, tumor growth was followed for 30-40 days by MRI. Tumor masses of boron treated mice increased markedly slowly than the control group. From the clinical editor: In this article, the authors described an improvement to existing boron neutron capture therapy. The dual MRI/BNCT agent, carried by LDLs, was able to maximize the selective uptake of boron in tumor cells, and, at the same time, quantify boron distribution in tumor and in other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor cell killing after neutron irradiation.

The current status and novel advances of boron neutron capture therapy clinical trials.

Boron neutron capture therapy (BNCT) is a treatment method that focuses on improving the cure rate of patients with cancer who are difficult to treat using traditional clinical methods. By utilizing the high neutron absorption cross-section of boron, material rich in boron inside tumor cells can absorb neutrons and release high-energy ions, thereby destroying tumor cells. Owing to the short range of alpha particles, this method can precisely target tumor cells while minimizing the inflicted damage to the surrounding normal tissues, making it a potentially advantageous method for treating tumors. Globally, institutions have progressed in registered clinical trials of BNCT for multiple body parts. This review summarized the current achievements in registered clinical trials, Investigator-initiated clinical trials, aimed to integrate the latest clinical research literature on BNCT and to shed light on future study directions.