Boron containing macromolecules and nanovehicles as delivery agents for neutron capture therapy.
Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive boron-10 is irradiated with low energy thermal neutrons to yield high linear energy transfer (LET) alpha particles ((4)He) and recoiling lithium -7((7)Li) nuclei. For BNCT to be successful, a sufficient number of (10)B atoms ( approximately 10(9) atoms/cell) must be selectively delivered to the tumor and enough thermal neutrons must be absorbed by them to sustain a lethal (10)B(n, alpha) (7)Li capture reaction. BNCT primarily has been used to treat patients with brain tumors, and more recently those with head and neck cancer. Two low molecular weight (LMW) boron delivery agents currently are being used clinically, sodium borocaptate and boronophenylalanine. However, a variety of high molecular weight (HMW) agents consisting of macromolecules and nanovehicles have been developed. This review will focus on the latter which include: monoclonal antibodies, dendrimers, liposomes, dextrans, polylysine, avidin, folic acid, and epidermal and vascular endothelial growth factors (EGF and VEGF). Procedures for introducing boron atoms into these HMW agents and their chemical properties will be discussed. In vivo studies on their biodistribution will be described, and the efficacy of a subset of them, which have been used for BNCT of tumors in experimental animals, will be discussed. Since brain tumors currently are the primary candidates for treatment by BNCT, delivery of these HMW agents across the blood-brain barrier presents a special challenge. Various routes of administration will be discussed including receptor-facilitated transcytosis following intravenous administration, direct intratumoral injection and convection enhanced delivery by which a pump is used to apply a pressure gradient to establish bulk flow of the HMW agent during interstitial infusion. Finally, we will conclude with a discussion relating to issues that must be addressed if these HMW agents are to be used clinically.
Wu
Gong
G
Department of Pathology, The Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, Ohio 43210, USA.
Barth
Rolf F
RF
Yang
Weilian
W
Lee
Robert J
RJ
Tjarks
Werner
W
Backer
Marina V
MV
Backer
Joseph M
JM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001896:Boron Compounds / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000532:radiotherapy; D002352:Carrier Proteins / Q000187:drug effects; D050091:Dendrimers / Q000627:therapeutic use; D003911:Dextrans / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods; D066246:ErbB Receptors / Q000187:drug effects; D058973:Folate Receptors, GPI-Anchored; D005909:Glioblastoma / Q000532:radiotherapy; D005910:Glioma / Q000532:radiotherapy; D006801:Humans; D008081:Liposomes / Q000627:therapeutic use; D046911:Macromolecular Substances / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D001896:Boron Compounds; D002352:Carrier Proteins; D050091:Dendrimers; D003911:Dextrans; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D066246:ErbB Receptors