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

Abstract

The clinical applications of positron emission tomography (PET) imaging pharmaceuticals have increased tremendously over the past several years since the approval of fluorine-fluorodeoxyglucose (F-FDG) by the Food and Drug Administration (FDA). Numerous F-labeled target-specific potential imaging pharmaceuticals, based on small and large molecules, have been evaluated in preclinical and clinical settings.F-labeling of organic moieties involves the introduction of the radioisotope by C-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-F bond formation as these reactions involve harsh conditions, including organic solvents, high temperature, and nonphysiological conditions. Several approaches, including F-labeled prosthetic groups, silicon, boron, and aluminum fluoride acceptor chemistry, and click chemistry have been developed, in the past, forF 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 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 theF radiochemistry and F-labeling methodologies for small molecules and target-specific biomolecules, a comprehensive review of coordination chemistry of Al, F-AlF labeling of peptide and protein conjugates, and evaluation ofF-labeled biomolecule conjugates as potential imaging pharmaceuticals.

Automated GMP compliant production of [18F]AlF-NOTA-octreotide

“…In this method, fluorine is firmly bound to Al 3+ forming [ 18 F] AlF which is then complexed by a suitable chelator, conjugated to a vector molecule of interest (e.g. octreotide) (Kumar and Ghosh 2018).…”

Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

“…An alternative strategy, which allows direct labelling of peptides and proteins, is based on the introduction of aluminium fluoride species "AlF" (for an overview, see [44]). This approach uses the strong binding of fluorine to aluminium and allows labelling via chelating systems, according to the labelling with radiometals.…”

“…This approach uses the strong binding of fluorine to aluminium and allows labelling via chelating systems, according to the labelling with radiometals. Several chelating moieties have been studied, of whom NOTA derivatives might be the best choice, yet [44]. A variety of peptide structures have been labelled using this method.…”

A review of approaches to 18F radiolabelling affinity peptides and proteins

“…Two types of 18 F acceptor chemistry used to radiolabel APPs will be discussed: ([ 18 F]AlF) 2+ complexation and isotopic exchange. The authors refer readers to a recent review of recent 18 F radiochemistry advances, which includes 18 F acceptor approaches and also a review of ([ 18 F]AlF) 2+ coordination chemistries by Kumar et al…”