Molecular therapy of human neuroblastoma cells using Auger electrons of indium-111-N-myc antisense oligonucleotide

1803 Objectives: Auger electrons break nucleic acids in the close vicinity, and thus therapeutic effect of Auger electrons of indium-111 (111In)-phosphorothioate antisense oligonucletides on human neuroblastoma cells with N-myc overexpression was investigated. Methods: Human neuroblastoma cells of SK-N-DZ (5 X 106 cells) were treated for 20 hrs with cationic reverse-phase vesicles encapsulating 111In-antisense oligonucleotides (AS) (average specific radioactivity of vesicles of 40 MBq/2 nmol of oligonucleotides/μmol of total phospholipids) with average diameter of 250 nm. N-myc expression and cell proliferation of treated cells were investigated as well as existence of 111In-AS hybridized with N-myc mRNA in treated cells. Tumorigenecity of treated cells was analyzed in nude mice. As a control, non-radiolabeled AS or 111In-sense oligonucleotides (S) were employed. Results: 111In-AS which hybridized with N-myc mRNA were detected from cells at 12 and 24 hrs after initiation of the treatment. Reduction in N-myc expression (average 27% to control) and inhibited cell proliferation (average 59% to control) were shown in cells at 48 hrs after treatment of 111In-AS. However, N-MYC-suppressed cells continued to produce tumor although a decrease in average weight of tumors was demonstrated in intraperitoneal cavity of nude mice. Neither of non-radiolabeled AS nor 111In-S caused any effect in cells. Conclusions: Auger electrons of 111In in the close vicinity of their target N-myc mRNA may cause reduction of cell proliferation rate of human neuroblastoma cells with N-myc overexpression, and it could potentially be a tool for internal molecular radiotherapy at a level of mRNA of a tumor cell.