Boron neutron capture therapy (BNCT) and photon activation therapy (PAT) are two radiotherapeutic modalities in which stable target atoms attached to cancer seeking compounds are activated by a beam of thermal neutrons for the former, and by photons for the latter. The result with both is the delivery of a dose of radiation to the tumor which exceeds that to normal tissues. The radiation delivered to the tumor is high LET by virtue of heavy particles in BNCT and Auger electrons in PAT. Of key importance is that Auger electron emission can be stimulated by thermal neutron capture, with resultant internal conversion of orbital electrons. Copious Auger cascades can be stimulated by this process, particularly if a target atom such as gadolinium-157, which has a unique thermal neutron cross section of 255,000 barns, is used. l57Gd has been attached to a tumor seeking porphyrin which also is tagged with boron. This development holds forth the promise of being able to apply, to a single tumor, the substantial advantages of both BNCT and Auger Electron Therapy (AET). The objective of this proposal is to exploit this potential, particularly in the medical management of patients with malignant brain tumors such as glioblastoma multiform. To evaluate the overall approach, l57Gd, attached to the porphyrin will be tested and compared it with 10B attached to the porphyrin. Comparison will then be made using the porphyrin with both l57Gd and 10B attached to the same molecule. To evaluate AET with Gd and thermal neutrons, a) vitro survival assays will be used to compare 10B and l57Gd as target atoms, b) Monte Carlo electron track structure codes will be used to confirm the local nature of the biological effects of 10B and l57Gd, and to predict dose, c) in vivo drug distribution studies will be used to optimize delivery of 10B and l57Gd to tumor, d) preliminary toxicity studies will be undertaken to evaluate the tolerance of the drug regimen established in (c), and e) AET and BNCT will be compared in therapy studies using both mice and rats.
