Radiobiology of BNCT mediated by GB-10 and GB-10+BPA in experimental oral cancer

Trivillin, Verónica A.; Heber, Elisa M.; Itoiz, M. E.; Nigg, David W.; Calzetta, Osvaldo; Longhino, Juan; Schwint, Amanda E.

doi:10.1016/j.apradiso.2004.05.015

Cited by 30 publications

(34 citation statements)

References 10 publications

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“…However, the therapeutic potential of the different administration protocols and boron compounds described here is suggested based on the biodistribution data and previous radiobiological studies in the hamster cheek pouch oral cancer model employing other boron carriers (e.g., Kreimann et al 2001b;Trivillin et al 2004;Pozzi et al 2009Molinari et al 2011). It is known that the biological effect of BNCT depends on the relative biological effectiveness factors (RBE) of the high-LET and low-LET dose components of BNCT.…”

Section: Discussionmentioning

confidence: 96%

“…We then demonstrated the therapeutic efficacy of BNCT mediated by BPA and/or GB-10 to treat experimental oral cancer in an experimental model in the hamster cheek pouch with no normal tissue radiotoxicity and without exceeding the radiotolerance of precancerous tissue (Kreimann et al 2001b;Trivillin et al 2004Trivillin et al , 2006Heber et al 2007;Pozzi et al 2009;Monti Hughes et al 2009). We also demonstrated the feasibility of treating spontaneous squamous cell carcinomas in felines with BNCT (Rao et al 2004;Trivillin et al 2008) and the efficacy of BNCT to inhibit the development of tumors from precancerous tissue (Monti ).…”

Section: Introductionmentioning

confidence: 97%

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Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

Heber

Kueffer

Lee

et al. 2012

Radiat Environ Biophys

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Boron neutron capture therapy (BNCT) combines selective accumulation of (10)B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na(3) [ae-B(20)H(17)NH(3)], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 97%

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

Heber

Kueffer

Lee

et al. 2012

Radiat Environ Biophys

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“…For comparison, data on the tumor response to BPA-mediated BNCT (23) have been included (Table 4C). Two arbitrary tumor size ranges (small: Ͻ10 mm 3 , large: Ն10 mm 3 ) were defined to categorize tumor size at the time of irradiation and evaluate a potential differential response according to size (31,34). The previously published BPA-BNCT data were reassessed to categorize tumor response as a function of tumor size.…”

Section: Tumor Responsementioning

confidence: 99%

“…This initial study (31) was primarily designed to evaluate safety and feasibility. It employed the thermalized epithermal neutron beam of the RA-6 Reactor at the Bariloche Atomic Center (32).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Success of Boron Neutron Capture Therapy (BNCT) Mediated by a Chemically Non-selective Boron Agent in an Experimental Model of Oral Cancer: A New Paradigm in BNCT Radiobiology

et al. 2006

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The hypothesis of boron neutron capture therapy (BNCT) research has been that the short-range, high-linear energy transfer radiation produced by the capture of thermal neutrons by (10)B will potentially control tumor and spare normal tissue only if the boron compound selectively targets tumor tissue within the treatment volume. In a previous in vivo study of low-dose BNCT mediated by GB-10 (Na(2)(10)B(10)H(10)) alone or combined with boronophenylalanine (BPA) in the hamster cheek pouch oral cancer model that was primarily designed to evaluate safety and feasibility, we showed therapeutic effects but no associated normal tissue radiotoxicity. In the present study, we evaluated the response of tumor, precancerous and normal tissue to high-dose BNCT mediated by GB-10 alone or combined with BPA. Despite the fact that GB-10 does not target hamster cheek pouch tumors selectively, GB-10-BNCT induced a 70% overall tumor response with no damage to normal tissue. (GB-10+BPA)-BNCT induced a 93% overall tumor response with no normal tissue radiotoxicity. Light microscope analysis showed that GB-10-BNCT selectively damages tumor blood vessels, sparing precancerous and normal tissue vessels. In this case, selective tumor lethality would thus result from selective blood vessel damage rather than from selective uptake of the boron compound.

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“…This treatment makes possible effective treatment of deep-lying tumors localized in the immediate vicinity of the spinal cord (e.g., lung tumor) [2]. In this context, considerable attention in recent investigations has been devoted to the biodistribution of sodium decahydrodecaborate (NaB 10 H 10 , GB-10) [11,12].…”

Section: Classification Of Boron Neutron Capture Therapy Agentsmentioning

confidence: 99%

Compounds for neutron capture therapy and their distribution in tumors and surrounding tissues of animals (A review)

Koryakin

2006

Pharm Chem J

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Boron-containing compounds for neutron capture therapy (NCT) can be divided into three groups: compounds without specific accumulation in tumor, tumor-selective compounds, and compounds capable of incorporating into the structure of tumor cells. For the NCT of cancer patients, sodium mercaptododecaborate (BSH) and p-boronophenylalanine (BPA) were selected from several hundred of boron-containing compounds. In this paper, data on the distribution of BSH and BPA in the organism of animals with model tumors modeling those encountered in oncological patients are reviewed. Methods for increasing the boron uptake in tumor, based on the combined use of boron compounds and modification factors such as hyperthermia, effect of electric pulses on the tumor zone, administration of compounds possessing vasodilating properties and influencing the blood-brain barrier permeability, are considered.Despite progress in the surgery, beam therapy, and chemotherapy, problems encountered in the treatment of malignant neoplasms such as cerebral glioblastoma multiforme, gliomas, melanomas, and their metastatic manifestations are still far from being solved, since all methods are usually equally damaging both tumor and intact cells in the zone of action. One direction in solving the task of selectively treating malignant neoplasms is related to the development of neutron capture therapy (NCT) [1,2]. The NCT method is based on the interaction of two factors: low-energy ( £ 0.025 eV) "thermal" neutrons and a tumoraffin (oncotropic) preparation delivering to the tumor a chemical element with large cross section for thermal neutron capture. A number of such elements exist in the nature, but only two have found use in the NCT due to their physicochemical properties: boron-10 ( 10 B, 3838 barn) and gadolinium-157 ( 157 Gd, 255 000 barn). The interaction of thermal neutrons with Gd atoms leads to the generation of internal-conversion electrons, instantaneous gamma radiation, and Auger electrons with a total energy of 7.94 MeV per decay event [3,4], all these particles possessing a rather large range in tumor tissues. Despite much lower neutron capture cross section, 10 B atoms offer a significant advantage in comparison to 157 Gd, since the products of the former neutron capture reaction -a particles and 7 Li recoil nuclei (Fig. 1) -have a short range comparable with the cell size, which ensures a local evolution of the reaction energy. For this reason, the use of boron-containing compounds capable of selectively accumulating in a tumor provides cell death after the 10 B(n, a, g) 7 Li reaction predominantly in the tumor cells. This circumstance together with low general toxicity of boron mostly account for the fact that the effort in NCT development since the very beginning was mostly devoted to the search for boron-containing compounds capable of delivering born in necessary amount to the tumor cells.Any candidate boron-containing compound for boron neutron capture therapy (BNCT) has to obey two main requirements:(i) Ability to accumulate predo...

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Radiobiology of BNCT mediated by GB-10 and GB-10+BPA in experimental oral cancer

Cited by 30 publications

References 10 publications

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

Therapeutic Success of Boron Neutron Capture Therapy (BNCT) Mediated by a Chemically Non-selective Boron Agent in an Experimental Model of Oral Cancer: A New Paradigm in BNCT Radiobiology

Compounds for neutron capture therapy and their distribution in tumors and surrounding tissues of animals (A review)

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