[Preparation and biodistribution of VIP-125I-ASON].
OBJECTIVE
To prepare VIP-125I-ASON and investigate the possibility of using it as an agent for diagnostic imaging and therapy of colon carcinoma.


METHODS
The iodination of a 15-base single-stranded antisense oligonucleotide (ASON) complementary to C-myc oncogene mRNA was carried out in the presence of TICl3. The radiolabeled oligonucleotide was complexed with a VIP-polylysine conjugate under certain condition. 3-5 microCi VIP-125I-ASON was injected into the tail vein of the BALB/c nude mice bearing transplanted HT29 colon carcinoma; the nude mice were killed at specific intervals after injection, and the biodistrbution of VIP-125I-ASON in the organs were calculated.


RESULTS
The biodistributed experiment showed that the 125I-ASON was excreted by kidney mostly and by liver and spleen in part. The results of studies after the injection of VIP-125I-ASON differed from those of unconjugated 125I-ASON. The conjugation of VIP to the ASON resulted in a decrease in the plasma clearance of the radiopharmaceutical, which may be due to the reduction in the renal clearance of the ASON. The highest uptake of tumor tissue (5.89% ID/g at 2 h) was significantly higher than that in nude mice given unconjugated ASON (P < 0.05). Tumor to blood ratios and tumor to muscle ratios were optimal at 4 h.


CONCLUSIONS
VIP-125I-ASON has desirable stability and higher uptake in tumor. It may provide a new sensitive mean for diagnostic antisense imaging and radiotherapy of tumor in the future.
Ou
Xiao-Hong
XH
Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Tan
Tian-Zhi
TZ
Li
Yun-Chun
YC
D000818:Animals; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution; D014660:Vasoactive Intestinal Peptide / Q000493:pharmacokinetics* / Q000627:therapeutic use
D007457:Iodine Radioisotopes; D016376:Oligonucleotides, Antisense; D019275:Radiopharmaceuticals; D014660:Vasoactive Intestinal Peptide