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Pharmacokinetic Characterization of Single-Stranded DNA in Murine Models Using High-Specific-Activity 68 Ga Radiolabeling Coupled with Dynamic Positron Emission Tomography

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide This study aimed to develop an efficient concentration methodology to enhance the specific activity of 68 Ga. By systematically optimizing chelation parameters, we established the relationships between the molar amounts of single-stranded DNA (A20) and varying 68 Ga specific activities, thereby maximizing the radiochemical yield in DNA radiolabeling systems. Method: The 68 Ga eluate was subjected to ionic enrichment and initially purified using cation-exchange chromatography, followed by concentration through an organic/aqueous phase protocol employing acetone/NaCl eluents. Systematic chelation experiments were performed by reacting gradient concentrations of A20 (1 or 3 nmol) with radiometal solutions at defined specific activities (1, 5, and 10 mCi/mL). The resulting reaction mixtures were subsequently purified using PD-10 columns. Dynamic PET/CT imaging of the purified 68 Ga-labeled A20 ( 68 Ga-A20) was performed over a 60 min interval to assess its biodistribution and metabolic kinetics in murine models. Results: Extraction of 68 Ga using water resulted in the introduction of sodium ions, which could interfere with subsequent labeling reactions. In contrast, acetone-based extraction effectively prevented contamination from exogenous ions. Optimization of the extraction protocol led to a 5-fold increase in the radioactivity concentration of 68 Ga. Labeling studies demonstrated an efficiency of 75.03% when 3 nmol (100 μM) of A20 was used, and the 68 Ga radioactivity concentration was maintained at 1 mCi/mL. Dynamic PET/CT imaging revealed that 68 Ga-A20 was predominantly eliminated via the renal pathway in healthy mice. Following curve-fitting analysis, the calculated half-lives were 6.61 ± 0.26 min in blood, 13.53 ± 1.04 min in kidney, and 7.61 ± 0.27 min in liver. Conclusion: This study demonstrated that the radioactivity concentration of 68 Ga can be effectively enhanced by processing the 68 Ga solution through cation-exchange chromatography followed by acetone extraction, representing a critical advancement in improving radiolabeling efficiency. Additionally, the results indicated that 68 Ga-A20 was primarily eliminated via the renal pathway in healthy mice.

Source: ACS Omega

DOI: 10.1021/acsomega.5c07282