title: Preferential accumulation within tumors and in vivo imaging by functionalized luminescent dendrimer lanthanide complexes.
abstract: We have created a dendrimer complex suitable for preferential accumulation within liver tumors and luminescence imaging by substituting thirty-two naphthalimide fluorophores on the surface of the dendrimer and incorporating eight europium cations within the branches. We demonstrate the utility and performance of this luminescent dendrimer complex to detect hepatic tumors generated via direct subcapsular implantation or via splenic injections of colorectal cancer cells (CC531) into WAG/RijHsd rats. Luminescence imaging of the tumors after injection of the dendrimer complex via hepatic arterial infusion revealed that the dendrimer complex can preferentially accumulate within liver tumors. Further investigation indicated that dendrimer luminescence in hepatic tumors persisted in vivo. Due to the incorporation of lanthanide cations, this luminescence agent presents a strong resistance against photobleaching. These studies show the dendrimer complex has great potential to serve as an innovative accumulation and imaging agent for the detection of metastatic tumors in our rat hepatic model.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Alcala
authors.forename: Chad M
authors.initials: CM
authors.lastname: Shade
authors.forename: Hyounsoo
authors.initials: H
authors.lastname: Uh
authors.forename: Shu Ying
authors.initials: SY
authors.lastname: Kwan
authors.forename: Matthias
authors.initials: M
authors.lastname: Bischof
authors.forename: Zachary P
authors.initials: ZP
authors.lastname: Thompson
authors.forename: Kristy A
authors.initials: KA
authors.lastname: Gogick
authors.forename: Adam R
authors.initials: AR
authors.lastname: Meier
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Strein
authors.forename: David L
authors.initials: DL
authors.lastname: Bartlett
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Modzelewski
authors.forename: Yong J
authors.initials: YJ
authors.lastname: Lee
authors.forename: Stéphane
authors.initials: S
authors.lastname: Petoud
authors.forename: Charles K
authors.initials: CK
authors.lastname: Brown
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D003952:Diagnostic Imaging / Q000379:methods*; D004586:Electrophoresis; D005063:Europium / Q000008:administration & dosage / Q000378:metabolism*; D066298:In Vitro Techniques; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D049449:Luminescence; D008297:Male; D051381:Rats; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D005063:Europium