Molecular imaging and pharmacokinetics of (99m) Tc-hTERT antisense oligonucleotide as a potential tumor imaging probe.

Targeting and visualization of human telomerase reverse transcriptase (hTERT) represents a promising approach for providing diagnostic value. The uptake kinetics and imaging results of (99m) Tc-hTERT antisense oligonucleotides (ASON) in hTERT-expressing cells were examined in vitro and in vivo. The pharmacokinetics and acute toxicity studies of (99m) Tc-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). Lipid carrier incorporation significantly increased the transmembrane delivery of radiolabeled probes (p < 0.05). hTERT-expressing xenografts in nude mice were clearly visualized at 6 h postinjection of the antisense probe but not the sense control probe. However, liposome did not increase the radioactivity accumulation of probes in tumors for either antisense or sense probe (p > 0.05). Radioactivity counts per minute versus time profiles for (99m) Tc-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 (99m) Tc-hTERT ASON in vivo. This study provides further evidences that (99m) Tc-hTERT ASON should be developed as a safe, potential molecular image-guided diagnostic agent.