Dynamic PET Imaging of EpCAM-Positive Colorectal Cancer Using Radiolabeled DTN-SYL3C Aptamer Conjugates

DNA tetrahedra (DTN) could enhance the circulation and targeting capabilities of aptamers. This study constructs a gallium-68 (⁶⁸Ga) radiolabeled DTN-SYL3C aptamer conjugate to evaluate their imaging potential for detecting epithelial cell adhesion molecule (EpCAM)-positive colorectal cancer (CRC). [⁶⁸Ga]-Ga-DTN-SYL3C was prepared by hybridizing T20-DTN-SYL3C with [⁶⁸Ga]-Ga-NOTA-ssDNA (A20) through base complementary pairing. Dynamic PET imaging was conducted in EpCAM-positive HT-29 tumor-bearing BALB/c nude mice using [⁶⁸Ga]-Ga-DTN and [⁶⁸Ga]-Ga-SYL3C as controls. T20-DTN-SYL3C was synthesized and characterized by agarose gel electrophoresis, while [⁶⁸Ga]-Ga-DTN-SYL3C was verified by high-performance liquid chromatography (HPLC). The radiolabeling yield of [⁶⁸Ga]-Ga-DTN-SYL3C was approximately 90%. Biodistribution studies indicated metabolism by the kidneys and liver. The blood half-life of [⁶⁸Ga]-Ga-DTN-SYL3C was 11.39 ± 2.66 min, longer than that of [⁶⁸Ga]-Ga-SYL3C (7.26 ± 0.17 min) in pharmacokinetic studies. Dynamic PET results showed tumor uptake of 0.89 ± 0.30%ID/g for [⁶⁸Ga]-Ga-DTN-SYL3C, 0.27 ± 0.22%ID/g for [⁶⁸Ga]-Ga-DTN, and 0.32 ± 0.16%ID/g for [⁶⁸Ga]-Ga-SYL3C at 1 h (<i>n</i> = 3). In conclusion, the [⁶⁸Ga]-Ga-labeled DTN-SYL3C aptamer conjugate effectively targets EpCAM-positive CRC and may serve as a promising imaging tool for detection and monitoring.