New compounds for neutron capture therapy (NCT) and their significance

Clearly the most effective tumor therapy would be obtained by the selective targeting of cytotoxic agents to tumor cells. Although many biomolecules are known to be taken up in tumors, the targeting of cytotoxic agents to tumors is limited by the fact that other essential cell pools compete with equal or even greater effectiveness. The approach of delivering stable non-toxic isotopes to tumor, with activation by means of an external radiation beam, is advantageous for two reasons: (1) it obviates problems associated with high uptake of isotopes in normal tissues, as these cell pools can be excluded from the radiation field, and (2) the general tumor area can be included in the activating beam field; thus, the possibility exists that all microscopic tumor extensions can be irradiated. As long as range of reaction products is short, dose will be restricted to the tumor, with a resultant high therapeutic ratio. This method can be accomplished with either photon activation therapy (PAT) or Neutron Capture Therapy (NCT), the latter will be emphasized here. The range of the high LET, low OER particles from the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction is approx. 10 ..mu..m, or one cell diameter; hence this reaction is optimal for cell killing. A number of biomolecules have been investigated as possible vehicles for transport of boron to tumors, including phenothiazines, thiouracils, porphyrins, nucleosides, and amino acids. Biodistributions of these compounds show selective concentration in tumor adequate for therapy. The biological halflives are in the order of days, allowing the possibility of fractionated or protracted irradiations. The radiobiological and physical implication of these parameters on NCT are discussed. The possibility of using an approximately-monoenergetic, scandium-filtered beam of about 2 keV, to reduce the dose from background radiations by about 85%, is also discussed. (ERB