Molecular imaging and pharmacokinetics of 99mTc-hTERT antisense oligonucleotide as a potential tumor imaging probe

摘要

Targeting and visualization of human telomerase reverse transcriptase (hTERT) represents a promising approach for providing diagnostic value. The uptake kinetics and imaging results of 99mTc-hTERT antisense oligonucleotides (ASON) in hTERT-expressing cells were examined in vitro and in vivo. The pharmacokinetics and acute toxicity studies of 99mTc-hTERT ASON were also performed. The labeling efficiencies of radiolabeled oligonucleotide reached 76?±?5%, the specific activity was up to 1850?kBq/μg, and the radiochemical purity was above 96%. Radioactivity accumulated to a higher concentration in hTERT-expressing cells with antisense probe than with sense control (p?0.05). Radioactivity counts per minute versus time profiles for 99mTc-hTERT ASON were biphasic, indicative of a three-compartment model. The pharmacokinetics parameters of half-life of distribution (T1/2α), half-life of elimination (T1/2β), total apparent volume of distribution (Vd), and total rate of clearance were 2.04?±?0.48?min, 24?±?4.8?min, 109.83?±?17.20?mL, and 3.19?±?0.17?mL/min, respectively. The acute toxicity study results showed the safe application of 99mTc-hTERT ASON in vivo. This study provides further evidences that 99mTc-hTERT ASON should be developed as a safe, potential molecular image-guided diagnostic agent.