Magnetic resonance tumor targeting imaging using gadolinium labeled human telomerase reverse tranase antisense probes.AbstractTo develop a molecular probe for MRI detection of human tumor telomerase reverse tranase （hTERT） mRNA expression. Uniformly phosphorothioate-modified hTERT antisense oligonucleotide （ASON） homing hTERT mRNA was labeled with gadolinium （Gd） through the bifunctional chelator 1,4,7, 10-tetraazacyclododecane-N, N', N'', N'''-tetraacetic acid （DOTA） stirred within 45 minutes at 60 °C. The Gd labeled probes were characterized in vitro. The cellular uptake rate and biodistribution of （99m） Tc-DOTA-ASON was measured instead of that of Gd-DOTA-ASON. A549 lung adenocarcinoma model was established in BALB/c nude mice and Gd-DOTA-ASON was injected intraperitoneally and MR images were acquired using 7.0T Micro-MRI （Bruker Biospec, Ettlingen, Germany） at different time points. Immunohistochemical analysis of telomerase activity of each xenograft was operated two days after in vivo imaging. The binding efficiency of Gd-DOTA-ASON reached as high as 71.7 ± 4.5% （n = 6）. Gd-DOTA-ASON displayed perfect stability in fresh human serum at 37 °C for 24 h. Compared with normal lung cells, A549 cells showed an obviously higher uptake of （99m） Tc-DOTA-ASON than that of lung cells （10.5 ± 2.7% vs. 4.8 ± 2.6%, P < 0.05）. The signal intensity of A549 xenografts can be enhanced by Gd-DOTA-ASON and the signal to noise ratio （SNR） of tumor to muscle reached 2.37 and maintained a relatively high level within 6 h after injection. The activity of hTERT in A549 tumors can be suppressed by Gd-DOTA-ASON in pathological slices. The results of this study show that Gd-DOTA-ASON can be a promising intracellular MR contrast probe for targeting telomerase-positive carcinomas. © 2012 Japanese Cancer Association. Cancer Sci. 2012 Aug;103（8）:1434-9. doi: 10.1111/j.1349-7006.2012.02316.x. Epub 2012 Jun 18. PMID: 22534012 [PubMed - indexed for MEDLINE]
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