Radioiodination of glycoprotein-conjugated liposomes by using the Bolton-Hunter reagent and biodistribution in tumor-bearing mice.

Abstract

We have developed a suitable radiolabeling method for our new type of glycoprotein-liposome conjugate (GCL), in order to investigate its potential utility as a drug carrier that can target the cellular functions of carbohydrate-binding proteins. In order to obtain radiolabeled GCL with high labeling efficiency, we introduced p-hydroxyphenylpropyl groups into the liposome membrane through the amine moiety of a constitutive phospholipid, dipalmitoylphosphatidylethanolamine (DPPE) by using Bolton-Hunter reagent (BHR). Radioiodination of the introduced tyrosyl groups was performed by the Chloramine-T method. The labeling efficiency of the BHR-treated liposome conjugate was high in comparison with that of the BHR-untreated liposome conjugate. An in vitro inhibition study showed that the binding affinity of 125I-labeled BHR-treated GCL (125I-F3S-BH) with lectin was twice as high as that of untreated conjugate (125I-F3S). The biodistribution of 125I-F3S-BH in mice was considerably different from that of 125I-F3S. 125I-F3S-BH was more rapidly taken up by the liver and was more rapidly excreted from the liver than 125I-F3S. Moreover, 125I-F3S-BH accumulated more rapidly into the kidneys, which resulted a lower radioactivity in the blood circulation at an earlier time point than in the case of 125I-F3S. The characteristics of tumor accumulation of 125I-F3S-BH and 125I-F3S were similar to those in blood. If F3S is to be employed as an in vivo targeting ligand in biodistribution studies, BHR would be a suitable tool for radiolabeling because it allows GCL to retain the biological activity and characteristics of the unmodified conjugate.

• Authors: N Shimura, Y Sogawa, Y Kawakita, M Ikekita, N Yamazaki, S Kojima
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 29 Issue 4 Pg. 491-6 (May 2002) ISSN: 0969-8051 [Print] United States
• PMID: 12031885 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Chloramines
• Drug Carriers
• Liposomes
• Radiopharmaceuticals
• Succinimides
• Tosyl Compounds
• alpha-Fetoproteins
• chloramine-T
• Bolton-Hunter reagent

Topics

• Animals
• Carcinoma, Ehrlich Tumor (diagnostic imaging, metabolism)
• Chloramines (chemistry)
• Drug Carriers (chemistry, pharmacokinetics)
• Isotope Labeling (methods)
• Liposomes (chemistry, pharmacokinetics)
• Male
• Mice
• Mice, Inbred Strains
• Models, Molecular
• Radionuclide Imaging
• Radiopharmaceuticals (pharmacokinetics)
• Sensitivity and Specificity
• Succinimides (chemistry)
• Tissue Distribution
• Tosyl Compounds (chemistry)
• alpha-Fetoproteins (chemistry, pharmacokinetics)