HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Watanabe, N. Articles by Sasaki, Y. Search for Related Content PubMed PubMed Citation Articles by Watanabe, N. Articles by Sasaki, Y.

Molecular Therapy of Human Neuroblastoma Cells Using Auger Electrons of ¹¹¹In-Labeled N-myc Antisense Oligonucleotides

¹ Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; ² Department of Chemistry, Gunma University Graduate School, Gunma, Japan; ³ Department of Radiopharmacy, School of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan; and ⁴ Division of Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Correspondence: For correspondence or reprints contact: Naoyuki Watanabe, MD, PhD, Division of Human Health, International Atomic Energy Agency, Wagramer Strasse 5, P.O. Box 200, Vienna A-1400, Austria. E-mail: N.Watanabe{at}iaea.org

Auger electrons can create breaks in nucleic acids, giving them possible therapeutic utility. We investigated the therapeutic effect of Auger electrons emitted by ¹¹¹In-labeled phosphorothioate antisense oligonucleotides on human neuroblastoma cells in which N-myc was overexpressed. Methods: Human SK-N-DZ neuroblastoma cells (5 x 10⁶ cells) were treated with cationic reverse-phase evaporation vesicles (REVs) encapsulating ¹¹¹In-labeled antisense (40 MBq/2 nmol of oligonucleotides/µmol of total phospholipids) that had an average diameter of 250 nm. Hybridization of the radiolabeled oligonucleotides with N-myc messenger RNA (mRNA), N-myc expression, and cell proliferation were investigated. The tumorigenicity of treated cells was analyzed in nude mice. Nonradiolabeled antisense, ¹¹¹In-labeled sense, or empty cationic REVs were used as controls. Results: ¹¹¹In-Labeled antisense, which hybridized with N-myc mRNA, was detected in cells at 12 and 24 h after the initiation of treatment. Reduced N-myc expression and inhibited cell proliferation were shown in the same cells at 48 h after the completion of treatment. N-myc expression–suppressed cells produced intraperitoneal tumors in nude mice, but the average weight of the tumors was lower than that of tumors in control mice. Conclusion: Auger electrons emitted from ¹¹¹In in close proximity to their target N-myc mRNA may prolong the time to cell proliferation in human neuroblastoma cells due to inhibition of the translation of N-myc. Auger electron therapy therefore has potential as an internally delivered molecular radiotherapy targeting the mRNA of a tumor cell.

Key Words: Auger electrons • human neuroblastoma • N-myc expression • cell proliferation • molecular radiotherapy

Related articles in JNM:

This Month in JNM

JNM 2006 47: 9a-10a. [Full Text]