[Use of 99mTc-survivin antisense oligonucleotide in diagnosis of hepatocellular carcinoma: an experiment with mice].

Objective: To investigate the possibility of using survivin antisense oligonucleotide (ASON) labeled with radionuclide technetium-99m ((99m)Tc) for diagnosing hepatocellular carcinoma in nude mice bearing human hepatoma.

Methods: A 18 mer single-stranded survivin ASON sequence was synthesized and linked with a primary amine on the 5'-end. Survivin ASON was labeled with (99m)Tc by conjugating the chelator, S-acetyl-NHS-MAG3 (mercaptoacetyltriglycine). The biodistribution, antisense gene imaging and antisense gene inhibition imaging of (99m)Tc-survivin ASON in nude mice bearing human hepatocellular carcinoma (SMMC-7721) were studied.

Results: Tumor lesion was early detected with (99m)Tc-survivin ASON and the lesion image showed up at 0.5 h postinjection. The accumulation of (99m)Tc-survivin ASON in tumor tissue gradually increased and reached the top at 4 h postinjection. The %ID/g (percentage of injected dose per gram of tissue) of (99m)Tc-survivin ASON in tumor tissue at 4 h postinjection was 0.69% +/- 0.11%. And the ratios of tumor to muscle were 3.35 +/- 0.57 in biodistribution study and 2.48 +/- 0.44 in antisense imaging study. But the %ID/g of (99m)Tc-survivin SON (sense oligonucleotide) in tumor tissue was only 0.17% +/- 0.01% at 4 h postinjection. And the ratios of tumor to muscle were 0.74 +/- 0.04 in biodistribution study and 1.15 +/- 0.36 in antisense imaging study. Both results of %ID/g of tumor tissue and ratio of tumor to muscle in SON group were significantly lower than those in ASON group at every check-time (P < 0.01). Furthermore, the tumor imaging was diminished in nude mice pretreated with unlabeled survivin ASON, and the ratio of tumor to muscle was only 0.93 +/- 0.23 at 4 h postinjection and significantly lower than 2.48 +/- 0.44 in nude mice untreated (P < 0.01).

Conclusion: The accumulation of (99m)Tc-survivin ASON in hepatocellular carcinoma tissue is specific. The antisense imaging with (99m)Tc-survivin ASON may be a promising method for diagnosis of hepatocellular carcinoma.