title: VIP grafted sterically stabilized liposomes for targeted imaging of breast cancer: in vivo studies.
abstract: Targeted delivery of radionuclides and therapeutic agents to specific biomarkers of breast cancer has important implications for the diagnosis and therapy of breast cancer. Vasoactive intestinal peptide receptors (VIP-R) are approximately five times more expressed in human breast cancer, compared to normal breast tissue. We have used VIP, a 28 amino acid mammalian neuropeptide, as a breast cancer targeting moiety for targeted imaging of breast cancer. VIP was covalently attached to the surface of sterically stabilized liposomes (SSL) that encapsulated a radionuclide, Tc99m-HMPAO. Rats with n-methyl nitrosourea (MNU)-induced in situ breast cancers were used to test this targeted liposomal imaging agent. Specifically, the pharmacokinetics and biodistribution of Tc99m-HMPAO encapsulating SSL with and without VIP were determined together with their ability to image breast cancer. The presence of VIP did not alter the size and Tc99m-HMPAO encapsulation ability of SSL. It also did not alter the pharmacokinetic profile of SSL. Long-circulating liposomes with and without VIP on their surface accumulated at significantly higher quantities in breast cancer when compared to normal breast, indicating passive targeting of these constructs to cancer tissues. Importantly, in breast cancer, Tc99m-HMPAO encapsulating SSL with VIP showed significantly more accumulation than SSL without VIP. The tumor to non-tumor ratio was also significantly higher for Tc99m-HMPAO encapsulating VIP-SSL than Tc99m-HMPAO encapsulating SSL without VIP, suggesting active targeting of VIP-SSL to breast cancer. Collectively, these data showed that Tc99m-HMPAO encapsulating VIP-SSL can be successfully used for the targeted imaging of breast cancer.
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612-7231, USA.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Dagar
authors.forename: Aparna
authors.initials: A
authors.lastname: Krishnadas
authors.forename: Israel
authors.initials: I
authors.lastname: Rubinstein
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blend
authors.forename: Hayat
authors.initials: H
authors.lastname: Onyüksel
mesh_terms: D000818:Animals; D002273:Carcinogens; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D007091:Image Processing, Computer-Assisted; D008081:Liposomes; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging*; D008770:Methylnitrosourea; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D010316:Particle Size; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D051381:Rats; D019690:Technetium Tc 99m Exametazime; D014018:Tissue Distribution; D014660:Vasoactive Intestinal Peptide / Q000138:chemical synthesis*
chemical_list: D002273:Carcinogens; D004337:Drug Carriers; D008081:Liposomes; D019275:Radiopharmaceuticals; D014660:Vasoactive Intestinal Peptide; D019690:Technetium Tc 99m Exametazime; D008770:Methylnitrosourea