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Boron neutron capture therapy delivery agents used in boron administration

Gales N. Laurentia, Anghel M. Rodica
Abstract: Boron neutron capture theory (BNCT) is a binary therapy applied in malignant tumours, resis-tant to other treatment methods, namely chemotherapy and radiotherapy. One of the main components is Bor-10, a stable isotope that can be inserted in the tumour cells by using specific transporters. Through the use of adequate Boron compounds, that preferably are located in the tumour cells and not in the healthy tissue, Boron neutron capture therapy provides a higher curative potential with minimal toxicity, at the level of normal tissues. In order to obtain a proper tumour control with minimum side effects, 10B increased concentrations should be obtained by selective cumulation within the tumour cells, with an adequate ion gradient between the normal and tumour tissues. Therapeutic effectiveness can be reached by a minimal boron concentration of 20-30 ppm inside the tumour and a tumour/blood and tumour/normal tissues boron concentration gradient of approximately 3. So far, clinical practice has used two main boron delivery agents: sodium borocaptate (Na2B12H11SH) (BSH) and a phenylalanine dihydroxy-boryl derivative, known as Boronophenylalanine (BPA). During the past 20 years, along with the development of new techniques of chemical synthesis and improved knowledge of biological and biochemical require-ments for the effectiveness of an agent and ways of boron delivery, a new number of boron delivery agents have appeared in response to the agents up to now. They include: aminoacids, nucleic acid precursors, DNA-binding molecules, porphyrin derivatives, high-molecular- weight delivery agents, macromolecules or nanovehicles such as monoclonal antibodies or monoclonal antibody fragments that bind to tumour epitopes- EGF, VEGF or liposomes, dendrimers, dextrans, polylysine, avidin, folic acid, etc. Next to the identification and study of new boron compounds or new compound combinations, other delivery methods are currently under research seeking to improve the classical intravenous administration and the selective intratumoral binding process as well as the therapeutic index (intraarterial, intratumoral administration, etc). Despite a large number of ongoing studies, a boron compound that fits all the ideal BNCT compound criteria has not yet been identified, especially in terms of tumour selectivity, the ratio of concentrations between the concentration in the tumour cells and the one in the normal cells, the delivery of a proper number of boron atoms in the tumour cells, hydrophilicity and lipophilicity, homogeneous intra-tumour distribution. The development of BNCT boron delivery agents has been initiated approximately 50 years ago and continues to represent at the same time a priority and a difficulty. Several bor-10 boron based pharmaceutical products have been prepared in view of their potential use in BNCT.

Keywords: Radiotherapy, BNCT, boron compounds


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