Scandium-44 has emerged as an attractive, novel PET radioisotope with a half-life and ideal emission properties (t1/2 = 3.97 h, Emean β+ = 632 keV) well matched to the pharmacokinetics of small molecules, peptides and small biologics. Conjugates of the current gold-standard chelator for 44Sc, 1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid (DOTA), require heating to achieve radiochemical complexation, limiting application of this isotope in conjunction with temperature-sensitive biologics. To establish Sc(III) isotopes as broadly applicable tools for nuclear medicine, development of alternative bifunctional chelators is required. We have developed and characterized the Sc(III)-chelation properties of the small-cavity triaza-macrocycle-based, picolinate-functionalized chelator H3mpatcn. Spectroscopic and radiochemical studies establish the [Sc(mpatcn)] complex as kinetically inert and appropriate for biological applications. A proof-of-concept bifunctional conjugate targeting the prostate-specific membrane antigen (PSMA), picaga-DUPA, chelates 44Sc to form 44Sc(picaga)-DUPA at room temperature with an apparent molar activity of 60 MBq/μmol and formation of inert RRR-Λ and SSS-Δ-twist isomers. We successfully employed 44Sc(picaga)-DUPA to image PSMA-expressing tumors in a preclinical mouse model. We also synthesized and evaluated the radiotherapeutic analogue 47Sc(picaga)-DUPA in mice bearing PSMA-positive xenografts and observed statistically significant slowing of tumor growth following the administration of 90 μCi 47Sc compound when compared to the saline cohort, thereby successfully establishing the theranostic pair. Finally, we also discuss homology of scandium and lutetium chelation chemistry in the context of the 44Sc/177Lu pair.

Establishing scandium chelation radiochemistry of azamacrocycle picolinates for theranostic applications with Sc-44/Sc-47

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.