title: The uptake of soluble and nanoparticulate imaging isotope in model liver tumours after intra-venous and intra-arterial administration.
abstract: Delivery of chemotherapeutic drugs to tumours by reformulation as nanoparticles has often been proposed as a means of facilitating increased selective uptake, exploiting the increased permeability of the tumour vasculature. However realisation of this improvement in drug delivery in cancer patients has met with limited success. We have compared tumour uptake of soluble Tc99m-pertechnetate and a colloid of nanoparticles with a Tc99m core, using both intra-venous and intra-arterial routes of administration in a rabbit liver VX2 tumour model. The radiolabelled nanoparticles were tested both in untreated and cationised form. The results from this tumour model in an internal organ show a marked advantage in intra-arterial administration over the intra-venous route, even for the soluble isotope. Tumour accumulation of nanoparticles from arterial administration was augmented by cationisation of the nanoparticle surface with histone proteins, which consistently facilitated selective accumulation within microvessels at the periphery of tumours.
authors.affiliation: Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics and Engineering, Australian National University, Australia. Electronic address: ross.stephens@anu.edu.au.
authors.forename: Ross W
authors.initials: RW
authors.lastname: Stephens
authors.affiliation: Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics and Engineering, Australian National University, Australia.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Knox
authors.affiliation: Animal Services Division, Research School of Biology, Australian National University, Australia.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Philip
authors.affiliation: Animal Services Division, Research School of Biology, Australian National University, Australia.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Debono
authors.affiliation: Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics and Engineering, Australian National University, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Bell
authors.affiliation: Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics and Engineering, Australian National University, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: King
authors.affiliation: Vascular Biology Laboratory, John Curtin School of Medical Research, Australian National University, Australia.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Parish
authors.affiliation: Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics and Engineering, Australian National University, Australia.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Senden
authors.affiliation: Sirtex Medical Ltd, Sydney, Australia.
authors.forename: Marcel R
authors.initials: MR
authors.lastname: Tanudji
authors.affiliation: Sirtex Medical Ltd, Sydney, Australia.
authors.forename: Jillean G
authors.initials: JG
authors.lastname: Winter
authors.affiliation: Sirtex Medical Ltd, Sydney, Australia.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Bickley
authors.affiliation: Sirtex Medical Ltd, Sydney, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Tapner
authors.affiliation: Sirtex Medical Ltd, Sydney, Australia.
authors.forename: Jian H
authors.initials: JH
authors.lastname: Pang
authors.affiliation: Sirtex Medical Ltd, Sydney, Australia.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Jones
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D007261:Infusions, Intra-Arterial / Q000379:methods*; D007275:Injections, Intravenous / Q000379:methods*; D007554:Isotopes / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000175:diagnosis*; D011817:Rabbits
chemical_list: D007554:Isotopes
keywords: Arterial administration; Imaging isotope; Liver cancer; Nanoparticle delivery; Vascular permeability