1. ¹Department of Nuclear Medicine, West China Hospital of Sichuan University, Sichuan Province, China
2. ²Department of Pharmaceutical, Sichuan University, Sichuan Province, China

Correspondence: Professor Tianzhi Tan, Department of Nuclear Medicine, West China Hospital, Guoxuexiang 37#, Chengdu 610041, China. E-mail: ouxiaohong2002@xinhuanet.com

Received 1 July 2004; Published online 3 December 2004.

Abstract

A 15-mer phosphorothioate antisense oligonuclide (ASON) complementary to the translation start region of the C-myc oncogene mRNA was radioiodinated to enhance its antitumor activity, and vasoactive intestinal peptide bound covalently polylysine (VIP-polylysine) was used as a carrier to deliver the oligonucleotide into VIP receptor-positive tumor cells. The antitumor activity of radioiodinated ASON conjugated to VIP-polylysine(VIP-¹³¹I-ASON) was investigated in athymic mice bearing HT29 tumor xenografts in comparison with unconjugated radioiodinated ASON(¹³¹I-ASON), unlabelled ASON (VIP-ASON) and scrambled oligonucleotide (VIP-¹³¹I-MON) conjugated to VIP-polylysine. Conjugation ¹²⁵I-ASON to VIP-polylysine resulted in a 5.6-fold decrease in the plasma clearance and a 3.4-fold increase in tumor uptake of the radiopharmaceutical. Athymic mice bearing HT29 tumor xenografts were treated with 4 weekly doses of VIP-¹³¹I-ASON and the antitumor effects were assessed by use of the slope of the tumor growth curve. VIP-¹³¹I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing tumor growth rate 9.67-, 7.90-fold more effectively than ¹³¹I-ASON and VIP-ASON at equivalent doses of ASON. Conversely, ¹³¹I-ASON, VIP-ASON or VIP-¹³¹I-MON caused no significant effect compared with the normal saline. These data indicated that use of a VIP-polylysine carrier greatly increased HT29 tumor uptake of ASON and treatment with the VIP-¹³¹I-ASON complexes resulted in tumor growth delay in human colon cancer xenograft.