Positron emission tomography (PET) has emerged as a pivotal non-invasive imaging technique in cancer biology, enabling molecular-level visualization of metabolic processes and pathological biomarkers. However, clinical PET contrast media face limitations in specificity and toxicity, driving the exploration of aptamers—single-stranded nucleic acid ligands selected via systematic evolution of ligands by exponential enrichment (SELEX) as promising targeting agents. Aptamers offer advantages including chemical synthesizability, thermal stability, small size (12–30 kDa), and rapid tissue diffusion, though their short plasma half-life (minutes) and nuclease susceptibility hinder clinical translation. This review summarizes recent preclinical advances in aptamer-based PET probes, focusing on their targeting of human epidermal growth factor receptor 2 (HER2), nucleolin (NCL), prostate-specific membrane antigen (PSMA), epidermal growth factor receptor (EGFR), and other cancer-associated markers. Radiolabeling strategies (e.g., nucleophilic substitution, click chemistry, hybridization) and their impacts on tracer stability and tumor uptake are discussed. Additionally, challenges (e.g., nuclease degradation, renal clearance) and opportunities (e.g., nucleotide modification, nanoparticle conjugation) for clinical translation are analyzed. With the continued efforts for clinical translation, aptamer-based PET imaging agents are poised to become a viable and versatile tool in the foreseeable future.
Guo et al. (Tue,) studied this question.