Optimization of Boron Neutron Capture Therapy for the Treatment of Undifferentiated Thyroid Cancer

Dagrosa, María Alejandra; Thomasz, Lisa; Longhino, Juan; Perona, Marina; Calzetta, Osvaldo; Rebagliati, Raúl Jiménez; Cabrini, R. L.; Kahl, Stephen B.; Juvenal, Guillermo; Pisarev, Mario A.

doi:10.1016/j.ijrobp.2007.04.061

Cited by 24 publications

(13 citation statements)

References 27 publications

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“…Extensive international efforts have been made by physicists, chemists, clinicians, and biologists for over 50 years focused on the development and testing of BNCT in the treatment of cancer (Barth et al, 2005; Coderre and Morris, 1999; Hatanaka, 1991; Kabalka et al, 2003; Kabalka and Yao, 2006; Li et al, 2006; Pellettieri et al, 2008). Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas, either cutaneous primaries or cerebral metastases of melanoma, and, more recently, head and neck and liver cancer (Barth et al, 2005; Pellettieri et al, 2008; Cordoso et al, 2007; Dagrosa et al, 2007; Kankaaranta et al, 2007; Wittig et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

Biological evaluation of boronated unnatural amino acids as new boron carriers

Kabalka

Yao

Marepally

et al. 2009

Applied Radiation and Isotopes

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There is a pressing need for new and more efficient boron delivery agents to tumor cells for use in boron neutron capture therapy (BNCT). A class of boronated unnatural cyclic amino acids has demonstrated a remarkable selectivity toward tumors in animal and cell culture models, far superior to currently used agents in clinical BNCT. One of these amino acids, 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC), has shown a tumor to blood ratio of 8 and a tumor to normal brain ratio of nearly 21 in a melanoma bearing mouse model. This work represents further biological characterization of this compound for tumor targeting in an EMT6 murine mammary carcinoma mouse model and a T98G human glioblastoma cell line. Female BALB/c mice bearing EMT6 tumors were injected with the fructose complex form of racemic mixtures of cis-and trans isomers of ABCPC in identical concentrations. Boron concentrations were measured in the tumor, blood, brain, skin, and liver tissues at 1, 3, and 5 hr post injection. These observations revealed a remarkable difference in racemic mixtures of cis and trans isomers in tumor targeting by boron. This implies that further separation of the L and D forms of this compound may enhance tumor targeting to an even higher degree than that provided by the racemic mixtures. Since the uptake measurements were made in homogenized tumor and normal tissues, little is known about the subcellular location of the boron arising from the various isomeric forms of the amino acid. To study subcellular delivery of boron from ABCPC in T98G human glioblastoma cells, we employed secondary ion mass spectrometry (SIMS) based technique of ion microscopy, which is capable of quantitatively imaging isotopic (elemental) gradients in cells and tissues at 500 nm spatial resolution. The T98G cells were exposed to the nutrient medium containing 100 ppm boron equivalent of a mixture of both L and D isomers of ABCPC in the form of a fructose complex for 1 hr. Following this treatment, the cells were fast frozen, freeze-fractured, and freeze-dried for SIMS analysis. Within an hour of exposure, ABCPC provided partitioning of intracellular to extracellular boron of 3/1. SIMS imaging revealed that boron from ABCPC was distributed throughout the cell, including the nucleus. This level of boron delivery within an hour of exposure is superior to p-boronophenylalanine (BPA) and sodium borocaptate (BSH), which have been previously studied by SIMS in the same cell line. These encouraging observations provide compelling support for further isomeric separations of ABCPC into the D and L forms for enhanced tumor targeting and continued testing of these compounds as new boron carriers in BNCT.

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Section: Introductionmentioning

confidence: 99%

Biological evaluation of boronated unnatural amino acids as new boron carriers

Kabalka

Yao

Marepally

et al. 2009

Applied Radiation and Isotopes

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“…tBid can permeabilize the mitochondria, resulting in mitochondrial outer membrane permeabilization [40]. As a final result, caspase 3 cleavage occurs after BNCT treatment in murine and human melanoma cells [24], [6] and in other tumor cells such as undifferentiated thyroid carcinoma [16].…”

Section: Resultsmentioning

confidence: 99%

“…The size measurement was converted into tumor volume by the equation: tumor volume = length × width 2 /0.52 [15]. Necropsies were performed 15 or 22 days after tumor inoculation (1 or 7 days after irradiation, respectively), according to the method of Dagrosa and co-workers [16]. The mice were euthanized by cervical dislocation and then necropsied.…”

Section: Methodsmentioning

confidence: 99%

Apoptosis through Bcl-2/Bax and Cleaved Caspase Up-Regulation in Melanoma Treated by Boron Neutron Capture Therapy

Faião-Flores

Coelho²,

Arruda‐Neto

et al. 2013

PLoS ONE

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Boron neutron capture therapy (BNCT) is a binary treatment involving selective accumulation of boron carriers in a tumor followed by irradiation with a thermal or epithermal neutron beam. The neutron capture reaction with a boron-10 nucleus yields high linear energy transfer (LET) particles, alpha and 7Li, with a range of 5 to 9 µm. These particles can only travel very short distances and release their damaging energy directly into the cells containing the boron compound. We aimed to evaluate proliferation, apoptosis and extracellular matrix (ECM) modifications of B16F10 melanoma and normal human melanocytes after BNCT. The amounts of soluble collagen and Hsp47, indicating collagen synthesis in the ECM, as well as the cellular markers of apoptosis, were investigated. BNCT decreased proliferation, altered the ECM by decreasing collagen synthesis and induced apoptosis by regulating Bcl-2/Bax in melanoma. Additionally, BNCT also increased the levels of TNF receptor and the cleaved caspases 3, 7, 8 and 9 in melanoma. These results suggest that multiple pathways related to cell death and cell cycle arrest are involved in the treatment of melanoma by BNCT.

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“…Nonetheless, a compact accelerator has been developed as an alternative to a nuclear reactor, and it can be installed in a hospital, thus facilitating the easy application of BNCT [ 76 ]. Dagrosa et al [ 77 – 79 ] reported the application of BNCT for undifferentiated TC in vitro and in an in vivo mouse model. However, the clinical advantages of BNCT in TC management remain unknown.…”

Section: Clinical Application Of Lat1-targeting Agentsmentioning

confidence: 99%

Amino Acid Transporters as Potential Therapeutic Targets in Thyroid Cancer

Enomoto

Hotomi

2020

Endocrinol Metab

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Thyroid cancer cells have a high amino acid demand for proliferation, invasion, and metastasis. Amino acids are taken up by thyroid cancer cells, both thyroid follicular cell and thyroid parafollicular cells (commonly called "C-cells"), via amino acid transporters. Amino acid transporters up-regulate in many cancers, and their expression level associate with clinical aggressiveness and prognosis. This is the review to discuss the therapeutic potential of amino acid transporters and as molecular targets in thyroid cancer.

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Optimization of Boron Neutron Capture Therapy for the Treatment of Undifferentiated Thyroid Cancer

Cited by 24 publications

References 27 publications

Biological evaluation of boronated unnatural amino acids as new boron carriers

Biological evaluation of boronated unnatural amino acids as new boron carriers

Apoptosis through Bcl-2/Bax and Cleaved Caspase Up-Regulation in Melanoma Treated by Boron Neutron Capture Therapy

Amino Acid Transporters as Potential Therapeutic Targets in Thyroid Cancer

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