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

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 (F-18-FDG) by the Food and Drug Administration (FDA). Numerous F-18-labeled target-specific potential imaging pharmaceuticals, based on small and large molecules, have been evaluated in predinical and clinical settings. F-18-labeling of organic moieties involves the introduction of the radioisotope by C-F-18 bond formation via a nudeophilic or an electrophilic substitution reaction. However, biomolecules, such as peptides, proteins, and oligonudeotides, cannot be radiolabeled via a C-F-18 bond formation as these reactions involve harsh conditions, induding organic solvents, high temperature, and nonphysiological conditions. Several approaches, induding F-18-labeled prosthetic groups, silicon, boron, and aluminum fluoride acceptor chemistry, and dick chemistry have been developed, in the past, for F-18 labeling of biomolecules. Linear and macrocyclic polyaminocarboxylates and their analogs and derivatives form thermodynamically stable and kinetically inert aluminum chelates. Hence, macrocydic polyaminocarboxylates have been used for conjugation with biomolecules, such as folate, peptides, affibodies, and protein fragments, followed by F-18-AlF chelation, and evaluation of their targeting abilities in predinical and clinical environments. The goal of this report is to provide an overview of the F-18 radiochemistry and F-18-labeling methodologies for small molecules and target-specific biomolecules, a comprehensive review of coordination chemistry of Al3+, F-18-AlF labeling of peptide and protein conjugates, and evaluation of F-18-labeled biomolecule conjugates as potential imaging pharmaceuticals.