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[Experimental study of 99mTc-antisense DNA for tumor imaging]
Chengzhong Fan1, D J Hnatowich
1Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China. Chengzhong.fan@yahoo.com
Abstract:
This study was performed to explore the feasibility of antisense imaging with radiolabeled antisense oligonucleotides DNA in tumored nude mice in vivo. Two different tumor cell lines, KB-G2 and KB-31,were used; both antisense and control sense DNAs were administrated intratumorally. The hybridization activities analysis of MAG3 conjugated DNAs oligonucleotides was demonstrated by Polyacrylamide Gel Electrophoresis. The whole body imaging was performed 22 h after administration of radiolabeled antisense and control sense DNAs at 1.0 microg DNAs (100 microCi) in 100 microl per animal. Then the animals were sacrificed at 24 h after administration and the organs and tissues were dissected and weighed; the radioactivity of each sample was detected by r-counter; injection dose percentage per gram tissue (%ID/g) was calculated and the biodistribution obtained. Both MAGS conjugated oligonucleotides DNAs and natural oligonucleotides DNAs have the same hybridization activities. The whole body images demonstrate improved targeting of antisense DNAs vs sense DNAs in the KB-G2 but not the KB-31 animals. Tumor levels in the KB-G2 animals were significantly higher for the antisense DNAs vs sense DNAs (14.7 vs 8.5% ID/g) while this difference (8.6 vs 4.3% ID/g) was insignificant in the KB-31 animals. Evidence for tumor targeting in vivo by an antisense in that mechanism has been obtained; statistically higher tumor accumulations of the 99mTc-antisense DNA were observed when compared to the control 99mTc-sense DNA. The successful localization of antisense DNA in tumor demonstrates that antisense tumor targeting in vivo is feasible even though improvement in tumor delivery and normal tissue clearance are needed for practical antisense imaging.
Insights
This study explored radiolabeled antisense oligonucleotide DNA for tumor imaging in mice. Antisense DNA showed feasible tumor targeting in vivo, particularly in KB-G2 tumors, suggesting potential for future diagnostic applications.
Area of Science:
- Molecular Biology
- Nuclear Medicine
- Oncology
Background:
- Antisense oligonucleotides (ASOs) offer targeted therapeutic potential.
- In vivo imaging of ASOs is crucial for assessing delivery and efficacy.
- Radiolabeling ASOs enables quantitative biodistribution and tumor targeting assessment.
Purpose of the Study:
- To evaluate the feasibility of using radiolabeled antisense DNA for in vivo tumor imaging.
- To compare the tumor targeting efficiency of antisense DNA versus sense DNA in different tumor models.
- To determine the biodistribution and hybridization activity of radiolabeled oligonucleotides.
Main Methods:
- Two human tumor xenografts (KB-G2, KB-31) in nude mice were used.
- Intratumoral administration of radiolabeled (99mTc-MAG3) antisense and sense DNA oligonucleotides.
- Whole-body imaging, tissue biodistribution analysis (%ID/g), and gel electrophoresis for hybridization activity.
Main Results:
- Radiolabeled antisense and sense DNA oligonucleotides exhibited similar hybridization activities.
- Whole-body imaging revealed enhanced targeting of antisense DNA in KB-G2 tumors but not KB-31 tumors.
- Significantly higher tumor accumulation (%ID/g) of antisense DNA was observed in KB-G2 (14.7% vs 8.5%) compared to sense DNA, with no significant difference in KB-31 tumors.
Conclusions:
- In vivo tumor targeting using radiolabeled antisense DNA is feasible.
- Statistically significant tumor accumulation of antisense DNA was demonstrated in the KB-G2 model.
- Further optimization of tumor delivery and normal tissue clearance is necessary for clinical translation of antisense imaging.
