title: Feasibility of poly(ethylene glycol) derivatives as diagnostic drug carriers for tumor imaging.
abstract: Poly(ethylene glycol) (PEG) is an artificial but biocompatible hydrophilic polymer that has been widely used in clinical products. To evaluate the feasibility of using PEG derivative itself as a tumor imaging carrier via an enhanced permeability and retention (EPR) effect, we prepared indium-111-labeled PEG ((111)In-DTPA-PEG) and indocyanine green (ICG)-labeled PEG (ICG-PEG) with PEG molecular weights of 5-40kDa and investigated their in vivo biodistribution in colon26 tumor-bearing mice. Thereafter, single-photon emission computed tomography (SPECT) and photoacoustic (PA) imaging studies were performed. The in vivo biodistribution studies demonstrated increased tumor uptake and a prolongation of circulation half-life as the molecular weight of PEG increased. Although the observed differences in in vivo biodistribution were dependent on the labeling method ((111)In or ICG), the tumor-to-normal tissue ratios were comparable. Because PEG-based probes with a molecular weight of 20kDa (PEG20) showed a preferable biodistribution (highest accumulation among tissues excised and relatively high tumor-to-blood ratios), an imaging study using (111)In-DTPA-PEG20 and ICG-PEG20 was performed. Colon26 tumors inoculated in the right shoulder were clearly visualized by SPECT 24h after administration. Furthermore, PA imaging using ICG-PEG20 also detected tumor regions, and the detected PA signals increased in proportion with the injected dose. These results suggest that PEG derivatives (20kDa) serve as robust diagnostic drug carriers for tumor imaging.
authors: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan; Medical Imaging Project, Corporate R&D Headquarters, Canon Inc., 3-30-2 Shimomaruko, Ohta-ku, Tokyo, 146-8501, Japan.
authors: Kengo
authors: K
authors: Kanazaki
authors: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan; Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
authors: Kohei
authors: K
authors: Sano
authors: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan; Biomedical Imaging Research Center, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.
authors: Akira
authors: A
authors: Makino
authors: Medical Imaging Project, Corporate R&D Headquarters, Canon Inc., 3-30-2 Shimomaruko, Ohta-ku, Tokyo, 146-8501, Japan.
authors: Fumio
authors: F
authors: Yamauchi
authors: Medical Imaging Project, Corporate R&D Headquarters, Canon Inc., 3-30-2 Shimomaruko, Ohta-ku, Tokyo, 146-8501, Japan.
authors: Atsushi
authors: A
authors: Takahashi
authors: Medical Imaging Project, Corporate R&D Headquarters, Canon Inc., 3-30-2 Shimomaruko, Ohta-ku, Tokyo, 146-8501, Japan.
authors: Tsutomu
authors: T
authors: Homma
authors: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
authors: Masahiro
authors: M
authors: Ono
authors: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan. Electronic address: hsaji@pharm.kyoto-u.ac.jp.
authors: Hideo
authors: H
authors: Saji
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D007205:Indium Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007208:Indocyanine Green / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging*; D004369:Pentetic Acid / Q000737:chemistry; D061088:Photoacoustic Techniques; D011092:Polyethylene Glycols / Q000737:chemistry*; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D014018:Tissue Distribution
chemical_list: D004396:Coloring Agents; D004337:Drug Carriers; D007205:Indium Radioisotopes; D011092:Polyethylene Glycols; D004369:Pentetic Acid; D007208:Indocyanine Green
keywords: Cancer diagnosis; Indocyanine green; Photoacoustic imaging; Poly(ethylene glycol); Single-photon emission computed tomography