Hao Zeng
C&EN Article Assignment 1
Title of C&EN Article: Imaging agent combines diagnostic and therapeutic
potential. Complex incorporates F-18 for PET imaging and Sc-47 for
radiotherapy Author: Celia Henry Arnaud (January 10, 2022)
Reference from original journal article:
Jennifer N. Whetter, Brett A. Vaughn, Angus J. Koller, and Eszter Boros;
“An Unusual Pair: Facile Formation and In Vivo Validation of Robust Sc–18F
Ternary Complexes for Molecular Imaging”. Angew. Chem. Int. Ed.
10.1002/anie.202114203
Summary and Analysis:
Celia Henry Arnaud reported to C&EN news (Jan. 10, 2022) on the
synthesis of a novel compound containing 18F and scandium (47Sc)
radiolabels as a theranostic pair, which can be used for both diagnostic
positron emission tomography (PET) imaging (with 18F) and radiotherapy
(with 47Sc). The desired complex was formed by reacting the Sc-18F
precursor with a macrocyclic chelator system. The advantages of the new
PET complex include stronger bonding of fluorine (18F) to scandium, and
easier in vitro preparation. In vivo mice experiment has demonstrated that
the 18F-Sc complex targets tumors expressing prostate specific membrane
antigen (PSMA). This article is pertinent to inorganic chemistry because it
focuses on the chemistry of establishing a new complex molecule with dual
radiolabels for theranostic purposes.
The research project was conducted by Dr. Eszter Boros group in the
Department of Chemistry, Stony Brook University. Specifically, from the
original article report, Dr. Boros’ lab first established a Sc-18F complex
[18F][ScF(mpatcn)]− employing direct fluorination of the open coordination
site of [Sc(mpatcn)(H2O)] complex with NH4F, followed by purification using
reverse-phase chromatography. In addition to conventional 1H NMR, the
research group also utilized 19F and 45Sc NMR spectroscopy to
characterize the [ScF(mpatcn)]- complex, and obtained similar data
compared to the previously published literature reports on Sc-F complex.
However, due to the low yield of product (<5%) using direct fluorination
method, the final compound was achieved by the in situ preformation of the
[18F][Sc-F] species followed immediately by the addition of macrocyclic
chelating ligand mpatcn, which produced high yield (>20%) of desired
complex at mild conditions (pH 4.5, 600C) without the need for organic
solvents.
While [18F][AlF] remains to be the most common clinical PET agent
for cancer diagnosis, the recent interest arises in searching for matched
isotopic pairs for both diagnosis and subsequent radiotherapy, the socalled theranostic strategy. In the original paper of C&EN report, Dr. Boros’
group described an elegant synthesis of [18F][Sc-F] complex under mild
aqueous conditions. The compound was found to be chemically stable,
exhibiting inertness against defluorination in vivo. Furthermore, preclinical
studies using small molecule peptide conjugate [18F]Sc-F(picaga)-DUPA in
mice models demonstrated good targeting of radiochemicals to the tumor
sites, as well as excellent direct biodistribution correlation with that of
[47Sc]Sc(picaga)-DUPA, which revealed the ideal suitability of the ternary
complex [18F]Sc-F(mpatcn)]- as a diagnostic tool for the 47Sc therapeutic
isotope. Therefore, the 18F/47Sc isotope pair can be used together as
chemically matched, viable theranostic pair in positron emission
tomography (PET) imaging and radiotherapy with significant clinical
indications and applications.