This study discusses the chemical perspectives of the [18F]F-PSMA probe, a pivotal tool in prostate cancer imaging. [18F]Fluorine, a positron emitter with a half-life of 109.8 minutes, is produced in a cyclotron by bombarding [18O]-enriched targets with protons. The chemistry of this isotope parallels that of stable fluorine, facilitating its use in positron emission tomography (PET). The synthesis of [18F]F-PSMA involves a nucleophilic substitution (SN1) reaction, where [18F]fluoride ion replaces a leaving group in the precursor molecule. Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells, making it a crucial target for imaging. PSMA-targeted radioligands, such as [68Ga]Ga-PSMA-11, [18F]F-DCFPyL, and [99mTc]Tc-PSMA-I&S, bind to the extracellular domain of PSMA, enabling precise imaging. The design of PSMA radiotracers incorporates specific targeting moieties, functional groups for radiolabeling, and linkers to maintain binding affinity and pharmacokinetics. Common linkers include aliphatic, aromatic, peptide-based, and polyethylene glycol structures, while functional groups like tosylate and PyTFP are used for efficient [18F]fluorination. This review aims to elucidate the main linker and reactions in order to optimize these components to improve imaging sensitivity and specificity in detecting prostate cancer.
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