RT Journal Article
SR Electronic
T1 Molecular Therapy of Human Neuroblastoma Cells Using Auger Electrons of <sup>111</sup>In-Labeled N-<em>myc</em> Antisense Oligonucleotides
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1670
OP 1677
VO 47
IS 10
A1 Watanabe, Naoyuki
A1 Sawai, Hiroaki
A1 Ogihara-Umeda, Izumi
A1 Tanada, Shuji
A1 Kim, E. Edmund
A1 Yonekura, Yoshiharu
A1 Sasaki, Yasuhito
YR 2006
UL http://jnm.snmjournals.org/content/47/10/1670.abstract
AB 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 × 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.