General Requirements For Boron Delivery Agents

A successful boron delivery agent should have (1) no or minimal systemic toxicity with rapid clearance from blood and normal tissues, (2) high tumor (approximately 20 mg 10B/g) and low normal tissue uptake, (3) high tumor to brain (T:Br) and tumor to blood (T:Bl) concentration ratios (greater than 3-4:1), and (4) persistence in the tumor for a sufficient period of time to carry out BNCT. At this time, no single boron delivery agent fulfills all of these criteria. However, as a result of new synthetic techniques and increased knowledge of the biological and biochemical requirements for an effective agent, multiple new boron agents have emerged and these are described in a special issue of Anti-Cancer Agents in Medical Chemistry (6, 2, 2006). The major challenge in their development has been the requirement for specific tumor targeting to achieve boron concentrations sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal-tissue toxicity. The selective destruction of GBM cells in the presence of normal cells represents an even greater challenge compared to malignancies at other anatomic sites.

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