As the most widely used clinical isotope, fluorine-18 is an indispensable tool in diagnostic cancer imaging with positron emission tomography (PET). However, incorporation via C-F bond formation often involves low-yielding, multi-step radiochemical syntheses in organic solvents, incompatible with biological targeting vectors. Current alternatives to C-F bond formation are hindered by production of low specific activity radiopharmaceuticals (B-F), incompatibility with aqueous solvents (Si-F) and low in vivo stability (Al-F and Ga-F). Furthermore, fluorine-18 lacks a chemically matched therapeutic isotope. To address this, we hypothesized that our previously developed chelation platform, H3mpatcn, shown to form robust coordination complexes with scandium radioisotopes, can also form stable Sc-F ternary complexes. To validate this hypothesis, we employed density functional theory calculations to assess the feasibility of forming a [ScF(mpatcn)]- complex, synthesized and characterized the complex using NMR, and carried out preliminary optimization of radiolabeling conditions to form the corresponding [18F]-[ScF] complex. A comparison of a prostate-specific membrane antigen (PSMA) targeted probe radiolabeled with Sc-18F or 47Sc demonstrates no statistically significant differences in biodistribution and tumor uptake in a mouse model of prostate cancer. Sc-18F ternary complexes can be formed in 100% aqueous media between 60-100 in 30 minutes, providing a convenient radiofluorination approach for targeted, 18F-based radiopharmaceuticals, and we propose that Sc-18F complexes can serve as an unusual diagnostic match for the therapeutic 47Sc isotope with excellent potential for clinical translation.

Facile formation and in vivo validation of robust Sc-18F ternary complexes for molecular imaging

ACS Spring 2022

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