Biodistribution of GB-10 ( ) compound for boron neutron capture therapy (BNCT) in an experimental model of oral cancer in the hamster cheek pouch

Heber, Elisa M.; Trivillin, Verónica A.; Nigg, David W.; Kreimann, Erica L.; Itoiz, M. E.; Rebagliati, Raúl Jiménez; Batistoni, Daniel A.; Schwint, Amanda E.

doi:10.1016/j.archoralbio.2003.10.003

Cited by 33 publications

(35 citation statements)

References 38 publications

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“…complete response) of 70-90% (e.g., Kreimann et al 2001b). In addition, MAC-TAC tumor/normal pouch tissue selectivity was greater than that reported for BPA and GB-10 in this model (Kreimann et al 2001a;Heber et al 2004), conceivably allowing for an improved therapeutic ratio between tumor and healthy tissues. Tumor retention times are considerably longer for MAC-TAC than for BPA and GB-10.…”

Section: Discussioncontrasting

confidence: 44%

“…In the specific case of experimental models, dose calculations are based on the mean values obtained from biodistribution studies in separate sets of animals (Kreimann et al 2001a). In this sense, it is important to bear in mind that large intra-tumor, intertumor, intra-tissue, and inter-subject variations in gross boron content values have been reported (e.g., Heber et al 2004Heber et al , 2006. These variations must be accounted for in dose calculation and dose prescription, to avoid exceeding the radiotolerance of the healthy tissues within the treatment volume.…”

Section: Introductionmentioning

confidence: 98%

“…In previous studies, we demonstrated that potentially therapeutic boron concentrations could be delivered to hamster cheek pouch tumors employing BPA and decahydrodecaborate (GB-10) as the boron delivery agents individually or in combination (e.g., Kreimann et al 2001a;Heber et al 2004Heber et al , 2006. 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).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussioncontrasting

confidence: 44%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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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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“…We also demonstrated that, unlike BPA (16), GB-10 was deposited homogeneously in different tumor areas, an asset when treating heterogeneous tumors. We also demonstrated high tumor levels of boron with combinations of GB-10 and BPA (26). A synergistic effect in terms of boron uptake seems to occur to some extent when both compounds are administered jointly.…”

Section: Introductionmentioning

confidence: 76%

“…In effect, we showed that GB-10 is able to deliver therapeutically useful amounts of boron, albeit not selectively, to hamster cheek pouch tumors (26). We also demonstrated that, unlike BPA (16), GB-10 was deposited homogeneously in different tumor areas, an asset when treating heterogeneous tumors.…”

Section: Introductionmentioning

confidence: 90%

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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Optimizing the Therapeutic Efficacy of Boron Neutron Capture Therapy (BNCT) for Different Pathologies

Schwint

Hughes

Garabalino

et al. 2018

Boron‐Based Compounds

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Biodistribution of GB-10 ( ) compound for boron neutron capture therapy (BNCT) in an experimental model of oral cancer in the hamster cheek pouch

Cited by 33 publications

References 38 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

Optimizing the Therapeutic Efficacy of Boron Neutron Capture Therapy (BNCT) for Different Pathologies

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