Laboratory for Translational Research in Imaging Pharmaceuticals, The Wright Center of Innovation in Biomedical Imaging, Department of Radiology , The Ohio State University , Columbus , Ohio 43212 , United States.
Bioconjug Chem. 2018 Apr 18;29(4):953-975. doi: 10.1021/acs.bioconjchem.7b00817. Epub 2018 Mar 9.
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, for 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 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 F 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 of F-labeled biomolecule conjugates as potential imaging pharmaceuticals.
过去几年来，自从食品和药物管理局（FDA）批准氟代脱氧葡萄糖（F-FDG）以来，正电子发射断层扫描（PET）成像药物的临床应用大大增加。已经在临床前和临床环境中评估了基于小分子和大分子的许多 F 标记的靶向潜在成像药物。有机部分的 F 标记涉及通过亲核或亲电取代反应通过 C-F 键形成引入放射性同位素。然而，生物分子，如肽、蛋白质和寡核苷酸，不能通过 C-F 键形成进行放射性标记，因为这些反应涉及苛刻的条件，包括有机溶剂、高温和非生理条件。过去，已经开发了几种方法，包括 F 标记的前体基团、硅、硼和铝氟化物受体化学以及点击化学，用于 F 标记生物分子。线性和大环多氨基羧酸及其类似物和衍生物形成热力学稳定且动力学惰性的铝配合物。因此，大环多氨基羧酸已用于与生物分子（如叶酸、肽、亲和体和蛋白质片段）缀合，然后进行 F-AlF 螯合，并在临床前和临床环境中评估其靶向能力。本报告的目的是提供小分子和靶向特定生物分子的 F 放射化学和 F 标记方法学的概述、Al 的配位化学、肽和蛋白质缀合物的 F-AlF 标记的全面综述，以及评估作为潜在成像药物的 F 标记生物分子缀合物。
