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J Nucl Med. 2008; 49 (Supplement 1):51P
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Oncology-Basic Science: Basic Science

In-vivo Models

The biodistribution of 99mTc labeled antisense MORF/carrier/streptavidin nanoparticles

Yi Wang1, Xinrong Liu1, Kayoko Nakamura2, Ling Chen1, Mary Rusckowski1 and Donald Hnatowich1

1 Radiology, University of Massachusetts Medical School, Worcester, Massachusetts; 2 Radiology, Keio University School of Medicine, Tokyo, Japan

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Objectives: We are developing a two-component delivery nanoparticle in which streptavidin serves as a bridge between a biotinylated and radiolabeled antisense oligomer and a biotinylated carrier peptide such as tat. No evidence of inhibited function of the antisense oligomer or carrier due to the streptavidin has been observed and cellular accumulations of 99mTc labeled antisense MORF oligomer was improved by a factor of 11 by this nanoparticle. We have now used this strategy to deliver an antisense MORF oligomer in vivo.

Methods: A biotinylated 99mTc radiolabeled 25-mer MORF oligomer with a base sequence antisense to the RIa mRNA and its sense control were incorporated into nanoparticles along with biotinylated tat or polyarginine carriers and the nanoparticles were administrated IV to both normal and to nude mice bearing SUM149 breast tumor xenografts.

Results: The biodistributions at 3 to 21 h show much higher normal tissue levels for both MORFs independent of carrier when administered as the nanoparticles compared to naked. However, a statistically significant higher accumulation of both antisense compared to sense nanoparticles was observed along with much higher tumor accumulations compared to historical naked controls.

Conclusions: Because of the dominance of streptavidin within the MORF nanoparticles, the clearance from circulation and from normal organs of the radiolabeled MORF was markedly slower and accumulations in liver and kidneys increased compared to naked. Nevertheless, the higher accumulation in tumor of the antisense compared to sense MORF was again preserved.





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