Fluorine‐18‐Labeled Nucleotide Analogs Targeting Ecto‐5'‐Nucleotidase (CD73) for Positron Emission Tomography Imaging of Solid Tumors
Abstract
ABSTRACT Ecto‐5’‐nucleotidase (CD73) is a potential new drug target for cancer immunotherapy. Its overexpression is associated with various aggressive cancers, including triple‐negative breast cancer (TNBC) and pancreatic cancer, making it a promising target for diagnostic imaging. Besides antibodies, small‐molecule CD73 inhibitors have been developed and are currently in clinical trials. This study aimed to develop and evaluate fluorine‐18 labeled high‐affinity CD73 inhibitors as tracers for the non‐invasive positron emission tomography (PET) imaging of CD73 expression in cancer. Two CD73 inhibitors were selected for radiolabeling based on their high potency (K i values of ca. 1 nM) and favorable pharmacokinetic properties, yielding [ 18 F]PSB‐19427 ([ 18 F] 1 ) and [ 18 F]MRS‐4648 ([ 18 F] 2 ). Ex vivo imaging studies on human breast cancer tissues indicated specific binding of both radiotracers. Subsequent in vivo studies proved [ 18 F] 1 to be superior due to its long elimination half‐life and its accumulation in TNBC and pancreatic cancer tissues, suggesting its potential as a versatile PET tracer for imaging of various solid tumors. Compared to [ 18 F]FDG, [ 18 F] 1 was superior in visualizing TNBC, offering potential advantages over [ 18 F]FDG in terms of specificity and diagnostic accuracy. Thus, [ 18 F] 1 is a PET tracer with outstanding properties suitable for broad application in cancer diagnosis and personalized medicine.
Article Details
Authors (24)
Clemens Dobelmann
European Institute for Molecular Imaging (EIMI) University of Muenster Münster Germany
Constanze C. Schmies
PharmaCenter Bonn Pharmaceutical Institute Pharmaceutical & Medicinal Chemistry University of Bonn Bonn Germany
Georg Wilhelm Rolshoven
PharmaCenter Bonn Pharmaceutical Institute Pharmaceutical & Medicinal Chemistry University of Bonn Bonn Germany
Mirko Scortichini
Molecular Recognition Section, Laboratory of Bioorganic Chemistry National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda Maryland USA
Stefan Wagner
Andreas Isaak
European Institute for Molecular Imaging (EIMI) University of Muenster Münster Germany
Riham M. Idris
PharmaCenter Bonn Pharmaceutical Institute Pharmaceutical & Medicinal Chemistry University of Bonn Bonn Germany
Jennifer Dabel
European Institute for Molecular Imaging (EIMI) University of Muenster Münster Germany
Lucie Grey
Institut Für Pharmazeutische und Medizinische Chemie University of Muenster Muenster Germany
Karolina Losenkova
Medicity Research Laboratory and InFLAMES Flagship University of Turku Turku Finland
Susanne Moschütz
Institute of Bioanalytical Chemistry Center for Biotechnology and Biomedicine Leipzig University Leipzig Germany
Haneen Al Hroub
PharmaCenter Bonn Pharmaceutical Institute Pharmaceutical & Medicinal Chemistry University of Bonn Bonn Germany
Antje Keim
Institute of Bioanalytical Chemistry Center for Biotechnology and Biomedicine Leipzig University Leipzig Germany
Sandra Höppner
European Institute for Molecular Imaging (EIMI) University of Muenster Münster Germany
Jouko Sandholm
Pia Boström
Maija Hollmén
Norbert Sträter
Sven Hermann
European Institute for Molecular Imaging (EIMI) University of Muenster Münster Germany
Gennady G. Yegutkin
Medicity Research Laboratory and InFLAMES Flagship University of Turku Turku Finland
Kenneth A. Jacobson
Molecular Recognition Section, Laboratory of Bioorganic Chemistry National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda Maryland USA
Sonja Schelhaas
European Institute for Molecular Imaging (EIMI) University of Muenster Münster Germany
Christa E. Müller
PharmaCenter Bonn and Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn
Anna Junker
European Institute for Molecular Imaging (EIMI) University of Muenster Münster Germany