Method for In Vivo Detection of Cell-Surface Disease Markers

Background:

The medical diagnostics industry has an urgent demand for efficient non-invasive biomarkers to diagnose and stage disease progression for cancer and Alzheimer's disease.  One solution to this demand was the development of bioorthogonal reagents, chemicals designed to work together for a specific chemical reaction in a living system without interfering with the native biochemical processes in the system.  This technology platform offers a bioorthogonal chemistry method for advanced PET imaging, applicable to solid tumors or brain protein plaques. Relevant Links:

• https://cen.acs.org/synthesis/Tautomerization-ensures-quality-clicks/101/i15
• Hydrazonyl Sultones as Stable Tautomers of Highly Reactive Nitrile Imines for Fast Bioorthogonal Ligation Reaction | Journal of the American Chemical Society (acs.org)
• https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202200175
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469592/pdf/nihms-1741492.pdf
• https://pubs.acs.org/doi/full/10.1021/jacs.8b00126

Technology Overview:

This University at Buffalo invention offers a pair of compatible reagents, one antibody-based cell-surface biomarker target and one small molecule PET tracer (radioligand, represented in Figure 1 as BCN), that combine to provide a high affinity, disease specific detection system.  This invention incorporates a new class of bioorthogonal reagents called hydrazonyl sulfates (HS) that serve as stable tautomers of nitrile imines (NI), which are highly reactive.  The novel chemical format of this innovative technology overcomes the largest limitation of current PET imaging systems, the high background signal due to extended in vivo half-life of current antibodies employed, offering increased sensitivity, as well as improved disease detection and staging for patients.

Advantages:

• HS display a broad range of aqueous stability and tunable reactivity in a 1,3-dipolar cycloaddition reaction
• 6-member HS structure is extraordinarily stable
• Two-part bioorthogonal system is modular so each reagent can be individually optimized
• Standardization of the radioligand allows one ¹⁸F tracer independent of the cell-surface marker targeted
• Reduced PET imaging background as radioligand is secreted in less than one hour

Applications:

• Diagnosis of disease 
• Staging of disease progression
• Research tool for PET imaging studies

Intellectual Property Summary:

PCT/US2024/012471 filed January 22, 2024.

Stage of Development:

Laboratory demonstration through in vitro studies and analytical chemical analysis.

Licensing Status:

Available for licensing or collaboration.

Figure 1: