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The clinical applications of positron emission tomography (PET) imaging pharmaceuticals have increased tremendously over the past several years since the approval of 18 fluorine-fluorodeoxyglucose ( 18 F-FDG) by the Food and Drug Administration (FDA). Numerous 18 F-labeled target-specific potential imaging pharmaceuticals, based on small and large molecules, have been evaluated in preclinical and clinical settings. 18 F-labeling of organic moieties involves the introduction of the radioisotope by C- 18 F bond formation via a nucleophilic or an electrophilic substitution reaction. However, biomolecules, such as peptides, proteins, and oligonucleotides, cannot be radiolabeled via a C- 18 F bond formation as these reactions involve harsh conditions, including organic solvents, high temperature, and nonphysiological conditions. Several approaches, including 18 F-labeled prosthetic groups, silicon, boron, and aluminum fluoride acceptor chemistry, and click chemistry have been developed, in the past, for 18 F labeling of biomolecules. Linear and macrocyclic polyaminocarboxylates and their analogs and derivatives form thermodynamically stable and kinetically inert aluminum chelates. Hence, macrocyclic polyaminocarboxylates have been used for conjugation with biomolecules, such as folate, peptides, affibodies, and protein fragments, followed by 18 F-AlF chelation, and evaluation of their targeting abilities in preclinical and clinical environments. The goal of this report is to provide an overview of the 18 F radiochemistry and 18 F-labeling methodologies for small molecules and target-specific biomolecules, a comprehensive review of coordination chemistry of Al 3+ , 18 F-AlF labeling of peptide and protein conjugates, and evaluation of 18 F-labeled biomolecule conjugates as potential imaging pharmaceuticals.

18F-AlF Labeled Peptide and Protein Conjugates as Positron Emission Tomography Imaging Pharmaceuticals

¹⁸F-AlF Labeled Peptide and Protein Conjugates as Positron Emission Tomography Imaging Pharmaceuticals