Chelator Development for PET and SPECT Imaging
Increasing availability of high energy, biomedical cyclotrons provides access to radiometals with properties suitable for PET imaging and radiotherapy. We are interested in exploring the the aqueous, radioactive coordination chemistry of early transition metals/pseudolanthanides, specifically Ga(III), Ti(IV), Zr(IV), Co(III) and Y(III), and applying this chemistry to the imaging and treatment of cancer. We employ a palette of spectroscopic, physical inorganic chemistry methods to characterize the to-date understudied, aqueous coordination chemistry of these Lewis acids. Most recently, we have begun to explore reactivity and chemical transformations on tracer scale.
Representative Publications
W. Lin, D. Śmiłowicz, M. A. Joaqui-Joaqui, A. Bera, Z. Zhong, E. Alucio-Sarduy, J. C. Mixdorf, T. E. Barnhart, J. W. Engle, E. Boros. “Controlling the Redox Chemistry of Cobalt Radiopharmaceuticals” Angew. Chem. Int. Ed. 2024, e202412357
J. N. Whetter, D. Śmiłowicz, E. Boros."Exploring Aqueous Coordination Chemistry of Highly Lewis Acidic Metals with Emerging Isotopes for Nuclear Medicine” Acc. Chem. Res. 2024, 57, 933-944
A. J. Koller, S. Saini, I.F. Chaple, M.A. Joaqui-Joaqui, B. M. Paterson, M. T. Ma, P. J. Blower, V. C. Pierre, J. R. Robinson, S. E. Lapi, E. Boros. A General Design Strategy Enabling the Synthesis of Hydrolysis-Resistant, Water-Stable Titanium(IV) Complexes. Angew. Chem. Int. Ed. 2022, in press. Also highlighted in ChemistryViews
B. A. Vaughn, S. H. Ahn, E. Aluicio-Sarduy, J. Devaraj, A. P Olson, J. W. Engle and E. Boros. Chelation with a Twist: A Bifunctional Chelator to Enable Room Temperature Radiolabeling and Targeted PET Imaging with Scandium-44. Chem. Sci. 2020. 11, 333-342
Theranostic Approach to Radiochelator Development
The term “theranostic” combines the terms therapeutics and diagnostics. In radiopharmaceuticals, this refers to a pharmaceutical platform capable of accommodating both imaging and therapeutic radioisotopes, typically metallic radioisotopes. However, true theranostic pairs where the same element has isotopes appropriate for both diagnostic and therapeutic purposes are rare, so we are interested in the exploration of chelators able to accommodate multiple radioisotopes. Our recent work has focused on the development of stable chelator systems in aqueous media for the Sc-44/F-18/Lu-177 triad, as well as Pd-103.
Representative Publications
Glaser O., Goerlach H., Salek M.V., Aluicio-Sarduy E., Gork M.J., Śmiłowicz D., Amason E.K., Barnhart T.E., Engle J.W., Boros E. “Evaluation of Bifunctional, PSMA-Targeted Triazamacrocycle-Picolinates Compatible with the 18F/44Sc/177Lu Isotope Triad” J. Med. Chem. 2025, 68, 24, 26234–26245.
Bera A, Glaser O.M., Aluicio-Sarduy E., Engle J.W., Meimetis L.G., Boros, E, Śmiłowicz D. “Adapting Solid Phase Radiometallation Photorelease (SPRP) to the Synthesis of 44Sc and 177Lu Radiopharmaceuticals”. Mol. Pharmaceutics, 2025, 22, 4137–4144.
C. A Kelderman, O. M. Glaser, J. N. Whetter, E. Alucio-Sarduy, J. C. Mixdorf, K. M. Sanders, I. A. Guzei, T. E. Barnahrt, J. W. Engle, E. Boros. “Charting the Coordinative Landscape of the 18F-Sc/44Sc/177Lu triad with the Tri-aza-cyclononane (tacn) Scaffold” Chem. Sci., 2024,15, 17927-17936
J. N. Whetter, B. A. Vaughn, A. J. Koller, E. Boros An Unusual Pair: Facile Formation and In Vivo Validation of Robust Sc-18F Ternary Complexes for Molecular Imaging. Angew. Chem. Int. Ed. 2022 in press Hot Paper, highlighted in C&EN News.