Recent Results with Liposomes as Boron Delivery Vehicles for Boron Neutron Capture Therapy

Hawthorne, M. Frederick; Feakes, Debra A.; Shelly, Kenneth

doi:10.1007/978-1-4757-9567-7_2

Cited by 12 publications

(14 citation statements)

References 8 publications

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“…The advantages of such compounds are that they potentially can deliver higher concentrations of boron to tumors without increased toxicity. (51,52). Boroncontaining dipeptides also have shown low toxicity and good tumor-localizing properties (53,54).…”

Section: Low Molecular Weight Agentsmentioning

confidence: 99%

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Barth

Coderre²,

Vicente³

et al. 2005

Clinical Cancer Research

908

666

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Background: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield high linear energy transfer A particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas and either cutaneous primaries or cerebral metastases of melanoma, most recently, head and neck and liver cancer. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the United States, Japan, several European countries, and Argentina. Accelerators also can be used to produce epithermal neutrons and these are being developed in several countries, but none are currently being used for BNCT. Boron Delivery Agents: Two boron drugs have been used clinically, sodium borocaptate (Na 2 B 12 H 11 SH) and a dihydroxyboryl derivative of phenylalanine called boronophenylalanine. The major challenge in the development of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations (f20 Ag/g tumor) sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal tissue toxicity. Over the past 20 years, other classes of boron-containing compounds have been designed and synthesized that include boroncontaining amino acids, biochemical precursors of nucleic acids, DNA-binding molecules, and porphyrin derivatives. High molecular weight delivery agents include monoclonal antibodies and their fragments, which can recognize a tumor-associated epitope, such as epidermal growth factor, and liposomes. However, it is unlikely that any single agent will target all or even most of the tumor cells, and most likely, combinations of agents will be required and their delivery will have to be optimized. Clinical Trials: Current or recently completed clinical trials have been carried out inJapan, Europe, and the United States. The vast majority of patients have had high-grade gliomas. Treatment has consisted first of ''debulking'' surgery to remove as much of the tumor as possible, followed by BNCTat varying times after surgery. Sodium borocaptate and boronophenylalanine administered i.v have been used as the boron delivery agents. The best survival data from these studies are at least comparable with those obtained by current standard therapy for glioblastoma multiforme, and the safety of the procedure has been established. Conclusions: Critical issues that must be addressed include the need for more selective and effective boron delivery agents, the development of methods to provide semiquantitative estimates of tumor boron content before treatment, improvements in clinical implementation of BNCT, and a need for randomized clinical trials with an unequivocal demonstration of therapeutic efficacy. If these issues are adequately addressed, then BNCTcould move forward as a treatment modality.

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Section: Low Molecular Weight Agentsmentioning

confidence: 99%

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Barth

Coderre²,

Vicente³

et al. 2005

Clinical Cancer Research

908

666

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“…Hawthorne and his associates have conceived and mounted a major effort to develop liposomes as a boron delivery agent to tumors. 164,[368][369][370][371][372][373][374] The concept was that since small unilamellar liposomes have been shown to penetrate the tumor cell membrane and localize intracellularly, incorporating boron compounds within such vesicles would provide a basis for achieving selectivity between tumor and normal cells. Initially, the boron compounds selected for incorporation into the aqueous core of the liposome were polyhedral borane anions such as B 10 H 10 2-, 2-NH 3 B 10 H 9 1-, and BSH.…”

Section: Liposomesmentioning

confidence: 99%

“…Initially, the boron compounds selected for incorporation into the aqueous core of the liposome were polyhedral borane anions such as B 10 H 10 2-, 2-NH 3 B 10 H 9 1-, and BSH. 368,369,374 Their rapid elimination from the tumor cell following deposition by the liposome prompted Hawthorne to use a boron species bearing an isocyanate group. This latter functionality has the capacity for becoming directly bound covalently to intracellular structures.…”

Section: Liposomesmentioning

confidence: 99%

The Chemistry of Neutron Capture Therapy

et al. 1998

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“…Other polyhedral borane anions with high boron content include derivatives of B 20 H 18 2À , although these compounds have shown little tumor specificity, and therefore may be better candidates for encapsulation into either targeted or nontargeted liposomes (52,53) and folate receptor targeting, boron containing polyamidoamino (PAMAM) dendrimers (54) and liposomes (55). Boron-containing dipeptides also have shown low toxicity and good tumor-localizing properties (56,57).…”

Section: Boron-containing Amino Acids and Polyhedral Boranesmentioning

confidence: 99%

“…This selectively targeted tumor blood vessels overexpressing VEGFR-2 in mice bearing 4T1 breast carcinoma. There also has been a longstanding interest on the use of boron-containing liposomes as delivery agents (52,53,126,127), but their size has limited their usefulness as brain tumor targeting agents, since they are incapable of traversing the BBB unless they have diameters <50 nm (128). If, on the other hand, they were administered intracerebrally or were linked to an actively transported carrier molecule (e.g., transferin), or alternatively if the BBB was transiently opened, these could be very useful delivery agents, especially for extracranial tumors (e.g., liver cancer).…”

Section: High Molecular Weight Agents Monoclonal Antibodies Other Rementioning

confidence: 99%