SUPPLEMENTARY INFORMATION:

The invention pertains to boramino acid compounds that can be used as imaging agents for positron emission tomography of cancer or for boron neutron capture therapy. Mimetics created by substituting the carboxylate group (-COO-) of an amino acid with trifluoroborate (-BF3-) are metabolically stable and allow for the use of fluorine-18 (¹⁸ F) as the radiolabel ( e.g., trifluoroborate phenylalanine (B-Phe)). Using boramino acid for¹⁸ F-labeling allows for integrating the¹⁸ F radiolabel into the core molecular backbone rather than the side-chains thus increasing the agent's target specificity. There is a direct relationship between amino acid uptake and cancer cell replication, where the uptake is extensively upregulated in most cancer cells. This uptake increases as cancer progresses, leading to greater uptake in high-grade tumors and metastases. Amino acids act as signaling molecules for proliferation and may also reprogram metabolic networks in the buildup of biomass. This invention provides for an unmet need for traceable amino acid mimics, including those based on naturally-occurring amino acids, which may be non-invasively detected by imaging technology, including for clinical diagnosis or BNCT. Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive boron-10 (¹⁰ B, approximately 20% of natural elemental boron), is irradiated and thus activated with neutrons of the appropriate energy to yield excited boron-11 (¹¹ B*). This isotope turn ( printed page 19985) decays into high energy alpha particles (“stripped” down⁴ He nuclei) and high energy lithium-7 (⁷ Li) nuclei. Both the emitted alpha particles and the lithium ions are close proximity reactions, i.e., at a range of approximately 5-9 µm; the diameter of a target cell. The energies produced in this ionization and radio-decay is cytotoxic and thus exploited as the basis for cancer radiotherapy. The success of BNCT is dependent on the selective delivery of sufficient amounts of¹⁰ B to the tumor site with only small amounts localized in the surrounding normal tissues thus sparing normal tissue from the nuclear capture and fission reactions.

The prospective exclusive license will be royalty bearing and will comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR 404.7. The prospective exclusive license may be granted unless, within fifteen (15) days from the date of this published notice, NIH receives written evidence and argument that establishes that the grant of the license would not be consistent with the requirements of 35 U.S.C. 209 and 37 CFR 404.7.

Properly filed competing applications for a license filed in response to this notice will be treated as objections to the contemplated license. Comments and objections submitted in response to this notice will not be made available for public inspection, and, to the extent permitted by law, will not be released under the Freedom of Information Act, 5 U.S.C. 552.