Unlocking the potential: phenylboronic acid as a nuclear-targeting boron agent for neutron capture therapy.

It has been proposed that boron neutron capture therapy (BNCT) holds promise as a treatment modality for melanoma. However, the effectiveness of boron agents in delivery remains a critical issue to be addressed for BNCT. To this end, phenylboronic acid, which exhibits good water solubility and low cytotoxicity similar to BPA, has been investigated as a potential nuclear-targeting boron agent. The boron concentration of phenylboronic acid was found to be 74.47 ± 12.17 ng/106 B16F10 cells and 45.77 ± 5.64 ng/106 cells in the nuclei. Molecular docking experiments were conducted to investigate the binding of phenylboronic acid to importin proteins involved in nuclear transport. The potential of phenylboronic acid to serve as a desirable nucleus-delivery boron agent for neutron capture therapy in melanoma warrants further exploration.

Impact of gadolinium concentration and cell oxygen levels on radiobiological characteristics of gadolinium neutron capture therapy technique in brain tumor treatment.

Neutron capture therapy (NCT) with various concentrations of gadolinium (157Gd) is one of the treatment modalities for glioblastoma (GBM) tumors. Current study aims to evaluate how variations of 157Gd concentration and cell oxygen levels can affect the relative biological effectiveness (RBE) of gadolinium neutron capture therapy (GdNCT) technique through a hybrid Monte Carlo (MC) simulation approach. At first, Snyder phantom including a spherical tumor was simulated by Geant4 MC code and relevant energy electron spectra to different 157Gd concentrations including 100, 250, 500, and 1000 ppm were calculated following the neutron irradiation of simulated phantom. Scored energy electron spectra were then imported to Monte Carlo damage simulation (MCDS) code to estimate RBE values (both RBESSB and RBEDSB) at different gadolinium concentrations and oxygen levels from 10 to 100%. The results indicate that variations of 157Gd can affect the energy spectrum of released secondary electrons including Auger electrons. Variation of gadolinium concentration from 100 to 1000 ppm in tumor region can change RBESSB and RBEDSB values by about 0.1% and 0.5%, respectively. Besides, maximum variations of 4.3% and 2% were calculated for RBEDSB and RBESSB when cell oxygen level changed from 10 to 100%. From the results, variations of considered gadolinium and oxygen concentrations during GdNCT can influence RBE values. Nevertheless, due to the not remarkable changes in the intensity of Auger electrons, a slight difference in RBE values would be expected at various 157Gd concentrations, although considerable RBE changes were calculated relevant to the oxygen alternations inside tumor tissue.

Development of a Gadolinium-Boron-Conjugated Albumin for MRI-Guided Neutron Capture Therapy.

Noninvasive monitoring of boron agent biodistribution is required in advance of neutron capture therapy. In this study, we developed a gadolinium-boron-conjugated albumin (Gd-MID-BSA) for MRI-guided neutron capture therapy. Gd-MID-BSA was prepared by labeling bovine serum albumin with a maleimide-functionalized gadolinium complex and a maleimide-functionalized closo-dodecaborate orthogonally. The accumulation of Gd-MID-BSA in tumors in CT26 tumor-bearing mice reached a maximum at 24 h after the injection, as confirmed by T1-based MRI and biodistribution analysis using inductively coupled plasma optical emission spectrometry. The concentrations of boron and gadolinium in the tumors exceeded the thresholds required for boron neutron capture therapy (BNCT) and gadolinium neutron capture therapy (GdNCT), respectively. The boron concentration ratios of tumor to blood and tumor to normal tissues satisfied the clinical criteria, indicating the reduction of undesired nuclear reactions of endogenous nuclei. The molar ratio of boron to gadolinium in the tumor was close to that of Gd-MID-BSA, demonstrating that the accumulation of Gd-MID-BSA in the tumor can be evaluated by MRI. Thermal neutron irradiation with Gd-MID-BSA resulted in significant suppression of tumor growth compared to the group injected with a boron-conjugated albumin without gadolinium (MID-BSA). The neutron irradiation with Gd-MID-BSA did not cause apparent side effects. These results demonstrate that the conjugation of gadolinium and boron within the albumin molecule offers a novel strategy for enhancing the therapeutic effect of BNCT and the potential of MRI-guided neutron capture therapy as a promising treatment for malignant tumors.

Stem cell-nanomedicine system as a theranostic bio-gadolinium agent for targeted neutron capture cancer therapy.

The potential clinical application of gadolinium-neutron capture therapy (Gd-NCT) for glioblastoma multiforme (GBM) treatment has been compromised by the fast clearance and nonspecific biodistribution of gadolinium-based agents. We have developed a stem cell-nanoparticle system (SNS) to actively target GBM for advanced Gd-NCT by magnetizing umbilical cord mesenchymal stem cells (UMSCs) using gadodiamide-concealed magnetic nanoparticles (Gd-FPFNP). Nanoformulated gadodiamide shielded by a dense surface composed of fucoidan and polyvinyl alcohol demonstrates enhanced cellular association and biocompatibility in UMSCs. The SNS preserves the ability of UMSCs to actively penetrate the blood brain barrier and home to GBM and, when magnetically navigates by an external magnetic field, an 8-fold increase in tumor-to-blood ratio is achieved compared with clinical data. In an orthotopic GBM-bearing rat model, using a single dose of irradiation and an ultra-low gadolinium dose (200 µg kg-1), SNS significantly attenuates GBM progression without inducing safety issues, prolonging median survival 2.5-fold compared to free gadodiamide. The SNS is a cell-based delivery system that integrates the strengths of cell therapy and nanotechnology, which provides an alternative strategy for the treatment of brain diseases.

Rational surface modification of gadolinium borate nanoparticles enhancing colloidal stability in physiological media for potential neutron capture therapy and magnetic resonance imaging.

Colloidal stability of nanomaterials in physiological media is an indispensable property for their biomedical applications. However, gadolinium borate (GdBO3) nanoparticles that hold promise as a theranostic agent for neutron capture therapy (NCT) and magnetic resonance imaging (MRI) of cancer tend to precipitate in phosphate buffered saline (PBS) owing to formation of insoluble gadolinium phosphate. To address this issue, in this work 10B-enriched GdBO3 nanoparticles were prepared and coated with mesoporous silica (mSiO2) of ~ 40 nm in thickness and subsequently grafted with hydrophilic polyglycerol (PG). The resulting GdBO3 @mSiO2-PG nanoparticles showed excellent colloidal stability in PBS due to the protection of the mSiO2 coating as well as superior dispersibility because of the high hydrophilicity of the PG layer. In vitro experiments revealed that GdBO3 @mSiO2-PG possessed low cytotoxicity and could be taken up by cancer cells in a concentration-dependent manner. In vivo studies indicated that GdBO3 @mSiO2-PG can circulate in mouse body for a considerably long time without obvious acute toxicity. In addition, GdBO3 @mSiO2-PG also showed promise as a T1-weighted MRI contrast agent with a proton longitudinal relaxivity of 0.67 mM-1 s-1. Our results indicate that GdBO3 @mSiO2-PG with enhanced colloidal stability in physiological media could serve as a promising multifunctional agent for cancer theranostics.

Design of a filtration system to improve the dose distribution of an accelerator-based neutron capture therapy system.

PURPOSE: The aim of this study is to design and evaluate a neutron filtration system to improve the dose distribution of an accelerator-based neutron capture therapy system. METHODS: An LiF-sintered plate composed of 99%-enriched 6 Li was utilized to filter out low-energy neutrons to increase the average neutron energy at the beam exit. A 5-mm thick filter to fit inside a 12-cm diameter circular collimator was manufactured, and experimental measurements were performed to measure the thermal neutron flux and gamma-ray dose rate inside a water phantom. The experimental measurements were compared with the Monte Carlo simulation, particle, and heavy ion transport code system. Following the experimental verification, three filter designs were modeled, and the thermal neutron flux and the biologically weighted dose distribution inside a phantom were simulated. Following the phantom simulation, a dummy patient CT dataset was used to simulate a boron neutron capture therapy (BNCT) irradiation of the brain. A mock tumor located at 4, 6, 8 cm along the central axis and 4-cm off-axis was set, and the dose distribution was simulated for a maximum total biologically weighted brain dose of 12.5 Gy with a beam entering from the vertex. RESULTS: All three filters improved the beam penetration of the accelerator-based neutron source. Filter design C was found to be the most suitable filter, increasing the advantage depth from 9.1 to 9.9 cm. Compared with the unfiltered beam, the mean weighted dose in the tumor located at a depth of 8 cm along the beam axis was increased by ∼25%, and 34% for the tumor located at a depth of 8 cm and off-axis by 4 cm. CONCLUSION: A neutron filtration system for an accelerator-based BNCT system was investigated using Monte Carlo simulation. The proposed filter design significantly improved the dose distribution for the treatment of deep targets in the brain.

In vivo evaluation of the effects of combined boron and gadolinium neutron capture therapy in mouse models.

While boron neutron capture therapy (BNCT) depends primarily on the short flight range of the alpha particles emitted by the boron neutron capture reaction, gadolinium neutron capture therapy (GdNCT) mainly relies on gamma rays and Auger electrons released by the gadolinium neutron capture reaction. BNCT and GdNCT can be complementary in tumor therapy. Here, we studied the combined effects of BNCT and GdNCT when boron and gadolinium compounds were co-injected, followed by thermal neutron irradiation, and compared these effects with those of the single therapies. In cytotoxicity studies, some additive effects (32‒43%) were observed when CT26 cells were treated with both boron- and gadolinium-encapsulated PEGylated liposomes (B- and Gd-liposomes) compared to the single treatments. The tumor-suppressive effect was greater when BNCT was followed by GdNCT at an interval of 10 days rather than vice versa. However, tumor suppression with co-injection of B- and Gd-liposomes into tumor-bearing mice followed by neutron beam irradiation was comparable to that observed with Gd-liposome-only treatment but lower than B-liposome-only injection. No additive effect was observed with the combination of BNCT and GdNCT, which could be due to the shielding effect of gadolinium against thermal neutrons because of its overwhelmingly large thermal neutron cross section.

Valproic Acid Enhances Radiosensitization via DNA Double-strand Breaks for Boronophenylalanine-mediated Neutron Capture Therapy in Melanoma Cells.

BACKGROUND: Boron neutron capture therapy (BNCT) is a radiotherapeutic approach that can destroy cancer cells while sparing the surrounding normal cells. Currently, boronophenylalanine (BPA) is the most common boron delivery agent used in BNCT for treating recurrent cancers of the head and neck, gliomas, and melanomas. On the other hand, valproic acid (VPA) is one of the representative class I histone deacetylase inhibitors (HDACi), which is a promising sensitizer for cancer therapies. In this study, we aimed to verify whether VPA could induce an enhanced effect in destroying melanoma cells in concurrence with BNCT and to explore the underlying mechanism of VPA-BNCT action in killing these cells. MATERIALS AND METHODS: Murine melanoma B16-F10 cells were pre-treated with VPA and irradiated with neutron during BPA-BNCT. We explored the clonogenic assay and the expression of phosphorylated H2AX (γH2AX) for cell survival and DNA double-strand breaks (DSBs), respectively. We also examined the expression levels of DNA damage responses-associated proteins and performed a cell cycle analysis. RESULTS: Our data indicated that the combination treatment of VPA and BNCT could significantly inhibit the growth of melanoma cells. Furthermore, VPA-BNCT treatment could exacerbate and perturb DNA DSBs in B16-F10 cells. In addition, pre-treatment of VPA abolished the G2/M arrest checkpoint caused by BNCT. CONCLUSION: Our results demonstrate that VPA has the potential to serve as a radiosensitizer of BPA-mediated BNCT for melanoma. These findings could improve BNCT treatments for melanoma.

SELECTION AND TESTING OF EXPERIMENTAL MODELS OF NORMAL AND MALIGNANT HUMAN CELLS IN VITRO AND EVALUATION OF THEIR SENSITIVITY RANGE TO THE NEUTRON/CAPTURE AND PHOTON/CAPTURE AGENTS AND PHOTOSENSITIZERS. / VIDBIR TA APROBUVANNIa EKSPERYMENTAL'NYKh MODELEI NORMAL'NYKh TA ZLOIaKISNYKh KLITYN LIuDYNY IN VITRO TA DOSLIDZhENIa MEZh ÏKhN'OÏ ChUTLYVOSTI DLIa NEITRONOZAKhVATNYKh, FOTON/ZAKhVATNYKh AGENTIV TA FOTOSENSYBILIZATORIV.

OBJECTIVE: to investigate the structural and morpho-functional changes in test systems of malignant (A-549 cellline) and normal (fibroblasts of the 6th passage) human cells during incubation with gadolinium-containing pho-ton-capture agent «Dotavist¼ and photosensitizer «Fotolon¼. METHODS: The passaged (continuously interweaved) cell culture technique on normal human fibroblasts and malig-nant human cells; cytological, biophysical, statistical methods. RESULTS: The cytotoxic properties of «Dotavist¼ gadolinium-containing photon-capturing agent and «Photolon¼photosensitizer in a wide range of concentrations (5, 10, 25, 50, 100 and 200 µl/ml) were studied by the morpho-functional characteristics (growth kinetics, proliferative and mitotic activity, presence of atypical cells) in the invitro test systems of malignant (non-small cell lung cancer cell line A-549) and normal (6th passage fibroblasts)human cells. It was found that the cytotoxic properties of «Dotavist¼ in test systems of malignant and normal cellsare expressed under its administration in high concentrations (100 and 200 µl/ml). During incubation with«Photolon¼ photosensitizer the cytotoxic effect on malignant cells was determined at the lowest concentrations (5and 10 µl/ml). Photosensitizer administration in the increasing concentrations has lead to genotoxic effects.Cytotoxic effect of photosensitizer on the normal human fibroblasts was evident in the 5-200 µl/ml concentrationrange. There was a moderate decrease in mitotic activity along with increasing concentration. Genotoxic propertiesof photosensitizer were evident at 25 µl/ml concentration and above. CONCLUSION: Study results of the effectiveness of neutron-capture and photon-capture technologies by the sensi-tivity assay in the in vitro test systems of human malignant cells (non-small cell lung cancer cell line A-549) andnormal cells (transplantable human fibroblast culture, the 6th passage) to the gadolinium-containing photon-cap-ture «Dotavist¼ agent and «Photolon¼ photosensitizer in different concentrations provide the basis for pre-clinicalstage of evaluating the effectiveness of medications used in binary technologies.

Moving Forward in the Next Decade: Radiation Oncology Sciences for Patient-Centered Cancer Care.

In a time of rapid advances in science and technology, the opportunities for radiation oncology are undergoing transformational change. The linkage between and understanding of the physical dose and induced biological perturbations are opening entirely new areas of application. The ability to define anatomic extent of disease and the elucidation of the biology of metastases has brought a key role for radiation oncology for treating metastatic disease. That radiation can stimulate and suppress subpopulations of the immune response makes radiation a key participant in cancer immunotherapy. Targeted radiopharmaceutical therapy delivers radiation systemically with radionuclides and carrier molecules selected for their physical, chemical, and biochemical properties. Radiation oncology usage of "big data" and machine learning and artificial intelligence adds the opportunity to markedly change the workflow for clinical practice while physically targeting and adapting radiation fields in real time. Future precision targeting requires multidimensional understanding of the imaging, underlying biology, and anatomical relationship among tissues for radiation as spatial and temporal "focused biology." Other means of energy delivery are available as are agents that can be activated by radiation with increasing ability to target treatments. With broad applicability of radiation in cancer treatment, radiation therapy is a necessity for effective cancer care, opening a career path for global health serving the medically underserved in geographically isolated populations as a substantial societal contribution addressing health disparities. Understanding risk and mitigation of radiation injury make it an important discipline for and beyond cancer care including energy policy, space exploration, national security, and global partnerships.

In vivo evaluation of PEGylated-liposome encapsulating gadolinium complexes for gadolinium neutron capture therapy.

Gadolinium neutron capture therapy (GdNCT) is a form of binary radiotherapy. It utilizes nuclear reactions that occur when gadolinium-157 is irradiated with thermal neutrons, producing high-energy γ-rays and Auger electrons. Herein, we evaluate the potential of GdNCT for cancer treatment using PEGylated liposome incorporated with an FDA-approved MRI contrast agent. The clinical gadolinium complex (Gadovist®) was successfully encapsulated inside the aqueous core of PEGylated liposomes by repeated freeze and thaw cycling. At a concentration of 152 µM Gd, the Gd-liposome showed high cytotoxicity upon thermal-neutron irradiation. In animal experiments, when a CT26 tumor model was administered with Gd-liposomes (19 mg 157Gd per kg) followed by 20-min irradiation of thermal neutron at a flux of 1.94 × 104 cm-2 s-1, tumor growth was suppressed by 43%, compared to that in the control group, on the 23rd day of post-irradiation. After two-cycle GdNCT treatment at a 10-day interval, tumor growth was more efficiently retarded. On the 31st day after irradiation, the weight of the excised tumor in the GdNCT group (38 mg 157Gd per kg per injection) was only 30% of that of the control group. These results demonstrate the potential of GdNCT using PEGylated liposomes containing MRI contrast agents in cancer treatment.

Biocompatible Iron-Boron Nanoparticles Designed for Neutron Capture Therapy Guided by Magnetic Resonance Imaging.

The combination of multiple functions in a single nanoparticle (NP) represents a key advantage of nanomedicine compared to traditional medical approaches. This is well represented by radiotherapy in which the dose of ionizing radiation should be calibrated on sensitizers biodistribution. Ideally, this is possible when the drug acts both as radiation enhancer and imaging contrast agent. Here, an easy, one-step, laser-assisted synthetic procedure is used to generate iron-boron (Fe-B) NPs featuring the set of functions required to assist neutron capture therapy (NCT) with magnetic resonance imaging. The Fe-B NPs exceed by three orders of magnitude the payload of boron isotopes contained in clinical sensitizers. The Fe-B NPs have magnetic properties of interest also for magnetophoretic accumulation in tissues and magnetic hyperthermia to assist drug permeation in tissues. Besides, Fe-B NPs are biocompatible and undergo slow degradation in the lysosomal environment that facilitates in vivo clearance through the liver-spleen-kidneys pathway. Overall, the Fe-B NPs represent a new promising tool for future exploitation in magnetic resonance imaging-guided boron NCT at higher levels of efficacy and tolerability.

Neutron activation of gadolinium for ion therapy: a Monte Carlo study of charged particle beams.

This study investigates the photon production from thermal neutron capture in a gadolinium (Gd) infused tumor as a result of secondary neutrons from particle therapy. Gadolinium contrast agents used in MRI are distributed within the tumor volume and can act as neutron capture agents. As a result of particle therapy, secondary neutrons are produced and absorbed by Gd in the tumor providing potential enhanced localized dose in addition to a signature photon spectrum that can be used to produce an image of the Gd enriched tumor. To investigate this imaging application, Monte Carlo (MC) simulations were performed for 10 different particles using a 5-10 cm spread out-Bragg peak (SOBP) centered on an 8 cm3, 3 mg/g Gd infused tumor. For a proton beam, 1.9 × 106 neutron captures per RBE weighted Gray Equivalent dose (GyE) occurred within the Gd tumor region. Antiprotons ([Formula: see text]), negative pions (- π), and helium (He) ion beams resulted in 10, 17 and 1.3 times larger Gd neutron captures per GyE than protons, respectively. Therefore, the characteristic photon based spectroscopic imaging and secondary Gd dose enhancement could be viable and likely beneficial for these three particles.

Influence of the particle size of gadolinium-loaded chitosan nanoparticles on their tumor-killing effect in neutron capture therapy in vitro.

Neutron capture therapy using 157Gd (Gd-NCT) is currently under development as a cancer radiotherapy. Melanoma cells were treated with gadolinium-loaded chitosan nanoparticles (Gd-nanoCPs) for Gd-NCT. Smaller Gd-nanoCPs had higher Gd content and better cellular association of Gd and thereby made the tumor-killing effect more efficient in comparison to larger Gd-nanoCPs. This indicates that Gd-nanoCP size reduction is an efficient method for improving the cellular affinity of Gd-nanoCPs and for enhancing the tumor-killing effect of Gd-NCT.

Image-Guided Neutron Capture Therapy Using the Gd-DO3A-BTA Complex as a New Combinatorial Treatment Approach.

Gadolinium-neutron capture therapy (Gd-NCT) is based on the nuclear capture reaction that occurs when 157Gd is irradiated with low energy thermal neutrons to primarily produce gamma photons. Herein, we investigated the effect of neutron capture therapy (NCT) using a small molecular gadolinium complex, Gd-DO3A-benzothiazole (Gd-DO3A-BTA), which could be a good candidate for use as an NCT drug due to its ability to enter the intracellular nuclei of tumor cells. Furthermore, MRI images of Gd-DO3A-BTA showed a clear signal enhancement in the tumor, and the images also played a key role in planning NCT by providing accurate information on the in vivo uptake time and duration of Gd-DO3A-BTA. We injected Gd-DO3A-BTA into MDA-MB-231 breast tumor-bearing mice and irradiated the tumors with cyclotron neutrons at the maximum accumulation time (postinjection 6 h); then, we observed the size of the growing tumor for 60 days. Gd-DO3A-BTA showed good therapeutic effects of chemo-Gd-NCT for the in vivo tumor models. Simultaneously, the Gd-DO3A-BTA groups ([Gd-DO3A-BTA(+), NCT(+)]) showed a significant reduction in tumor size (p < 0.05), and the inhibitory effect on tumor growth was exhibited in the following order: [Gd-DO3A-BTA(+), NCT(+)] > [Gd-DO3A-BTA(+), NCT(-)] > [Gd-DO3A-BTA(-), NCT(+)] > [Gd-DO3A-BTA(-), NCT(-)]. On day 60, the [Gd-DO3A-BTA(+), NCT(+)] and [Gd-DO3A-BTA(-), NCT(-)] groups exhibited an approximately 4.5-fold difference in tumor size. Immunohistochemistry studies demonstrated that new combinational therapy with chemo-Gd-NCT could treat breast cancer by both the inhibition of tumor cell proliferation and induction of apoptosis-related proteins, with in vivo tumor monitoring by MRI.

Design of drug delivery systems for physical energy-induced chemical surgery.

Physical energy-induced chemical surgery, a technique that induces antitumor effects by delivering a drug that exerts a therapeutic effect in response to physical energy and irradiating the diseased part with the corresponding physical energy, is a useful method to treat cancers with minimal systemic side effects. Among chemical surgery, photodynamic therapy (PDT) and neutron capture therapy (NCT) require a system that selectively delivers drugs to the diseased site. Although PDT and NCT have a similar concept, drug delivery systems (DDSs) for their purpose need different functions to solve the unique problems derived from the characteristics of respective physical energy. In this review, we will describe recent chemistry-based solutions including ours to overcome these challenges.

Practical aspects of 153Gd as a radioactive source for use in brachytherapy.

The goal of this study was to investigate the production, purification and immobilization techniques for a 153Gd brachytherapy source. We have investigated the maximum attainable specific activity of 153Gd through the irradiation of Gd2O3 enriched to 30.6% 152Gd at McMaster Nuclear Reactor. The advantage of producing 153Gd through this production pathway is the possibility to irradiate pre-sealed pellets of 152Gd enriched Gd2O3, thereby removing the need to perform chemical separation with large quantities of radio-impurities. However, small amounts of long-lived impurities are produced from the irradiation of enriched 152Gd targets due to traces of Eu in the sample. If the amount of impurities produced is deemed unacceptable, 153Gd can be isolated as an aqueous solution, chemically separated from impurities and loaded onto a sorbent with a high affinity for Gd before encapsulation.

Theranostic Nanoparticles Loaded with Imaging Probes and Rubrocurcumin for Combined Cancer Therapy by Folate Receptor Targeting.

The combination of different therapeutic modalities is a promising option to combat the recurrence of tumors. In this study, polylactic and polyglycolic acid nanoparticles were used for the simultaneous delivery of a boron-curcumin complex (RbCur) and an amphiphilic gadolinium complex into tumor cells with the aim of performing boron and gadolinium neutron capture therapy (NCT) in conjunction with the additional antiproliferative effects of curcumin. Furthermore, the use of Gd complexes allows magnetic resonance imaging (MRI) assessment of the amount of B and Gd internalized by tumor cells. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were targeted to ovarian cancer (IGROV-1) cells through folate receptors, by including in the formulation a PEGylated phospholipid functionalized with the folate moiety. NCT was performed on IGROV-1 cells internalizing 6.4 and 78.6 µg g-1 of 10 B and 157 Gd, respectively. The synergic action of neutron treatment and curcumin cytotoxicity was shown to result in a significant therapeutic improvement.

Insights into the use of gadolinium and gadolinium/boron-based agents in imaging-guided neutron capture therapy applications.

Gadolinium neutron capture therapy (Gd-NCT) is currently under development as an alternative approach for cancer therapy. All of the clinical experience to date with NCT is done with (10)B, known as boron neutron capture therapy (BNCT), a binary treatment combining neutron irradiation with the delivery of boron-containing compounds to tumors. Currently, the use of Gd for NCT has been getting more attention because of its highest neutron cross-section. Although Gd-NCT was first proposed many years ago, its development has suffered due to lack of appropriate tumor-selective Gd agents. This review aims to highlight the recent advances for the design, synthesis and biological testing of new Gd- and B-Gd-containing compounds with the task of finding the best systems able to improve the NCT clinical outcome.