Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Antisense oligonucleotide strategies in nuclear medicine

DJ Hnatowich PhD

Dept Radiology, University of Massachusetts Medical School, Worcester, MA,

Antisense targeting is being used to treat an increasing number of diseases. By contrast, the applications of antisense targeting in nuclear medicine for imaging or radiotherapy is in its infancy. AIMS METHODS RESULTS: The purpose of this contribution is to speculating upon those issues for which there are recent important results and/or revelations relating to antisense and nuclear medicine. One issue concerns the number of targeted mRNAs per cell. Estimates suggest that it may be difficult to image tissues in which the target gene is not overexpressed. Therefore, targets should be selected in favor of those in which the steady-state mRNA concentrations are highly elevated. In addition, DNAs must be chemically modified to accommodate the radiolabel. Therefore, it must be demonstrated that any chemical modification of antisense DNAs have not negatively influence those properties necessary for targeting. Finally, antisense strategies for therapy usually rely upon RNase H-mediated mechanisms. Targeting by this mechanism is followed by mRNA degradation. However, the loss of mRNA targets may be unfortunate for nuclear medicine applications. Accordingly, chemical forms of DNAs which are not substrates of RNase H should be considered for nuclear medicine applications of antisense targeting. CONCLUSION: The weight of evidence from in vitro, animal and patient investigations leave little doubt that, under certain circumstances at least, antisense DNAs are capable of intracellular mRNA targeting. A realistic test of antisense targeting for nuclear medicine applications will require that conditions be selected which optimize targeting for imaging rather than for therapy.

KEY WORDS: antisense imaging.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on anticancer strategies.