title: Magnetic resonance imaging of tumor with a self-traceable phosphorylcholine polymer.
abstract: Polymers are concentration-amplified with respect to the monomeric units. We show here that a phosphorylcholine polymer enriched with (13)C/(15)N at the methyl groups is self-traceable by multiple-resonance (heteronuclear-correlation) NMR in tumor-bearing mice inoculated with the mouse rectal cancer cell line (colon 26). Preliminary measurements indicated that the present polymeric nanoprobe was satisfactorily distinguished from lipids and detectable with far sub-micromolar spectroscopic and far sub-millimolar imaging sensitivities. Detailed ex vivo and in vivo studies for the tumor-bearing mice administered the probe with a mean molecular weight of 63,000 and a mean size of 13 nm, revealed the following: (1) this probe accumulates in the tumor highly selectively (besides renal excretion) and efficiently (up to 30% of the injected dose), (2) the tumor can thus be clearly in vivo imaged, the lowest clearly imageable dose of the probe being 100 mg/kg or 2.0 mg/20-g mouse, and (3) the competition between renal excretion and tumor accumulation is size-controlled; that is, the larger (higher molecular-weight) and smaller (lower molecular-weight) portions of the probe undergo tumor accumulation and renal excretion, respectively. The observed size dependence suggests that the efficient tumor-targeting of the present probe is stimulated primarily by the so-called enhanced permeability and retention (EPR) effect, that is, size-allowed invasion of the probe into the tumor tissue via defective vascular wall. Self-traceable polymers thus open an important area of magnetic resonance imaging (MRI) of tumors and may provide a highly potential tool to visualize various delivery/localization processes using synthetic polymers.
authors.affiliation: Advanced Biomedical Engineering Research Unit, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University , Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Yamada
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Imai
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takayama
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sugihara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuda
authors.forename: Hidehito
authors.initials: H
authors.lastname: Tochio
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shirakawa
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sando
authors.forename: Yu
authors.initials: Y
authors.lastname: Kimura
authors.forename: Akio
authors.initials: A
authors.lastname: Toshimitsu
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051379:Mice; D010767:Phosphorylcholine / Q000737:chemistry* / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism*
chemical_list: D011108:Polymers; D010767:Phosphorylcholine