title: PET imaging and biodistribution analysis of the effects of succinylated gelatin combined with L-lysine on renal uptake and retention of ⁶⁴Cu-cyclam-RAFT-c(-RGDfK-)₄ in vivo.
abstract: (64)Cu-cyclam-RAFT-c(-RGDfK-)4, an αVβ3 integrin-targeting tetrameric cyclic RGD peptide probe, is a potential theranostic compound for positron emission tomography (PET) of tumor angiogenesis and for internal radiotherapy owing to the multiple decay modes of (64)Cu. Since kidneys are dose-limiting organs in internal radiotherapy, we aimed to reduce the renal accumulation of (64)Cu-cyclam-RAFT-c(-RGDfK-)4 by co-injection with Gelofusine (GF), a succinylated gelatin solution, and/or L-lysine (Lys), and to explore, for the first time, the related mechanisms using the noninvasive and quantitative PET imaging technology. Biodistribution assays, dynamic and static PET scans, and metabolism studies with radio-thin-layer chromatography (radio-TLC) were performed in healthy or αVβ3-positive tumor-bearing mice. In the results, co-injection with GF markedly reduced the renal uptake and slightly increased the tumor uptake of (64)Cu-cyclam-RAFT-c(-RGDfK-)4. L-Lysine alone had no effect on the probe biodistribution, but the combined use of Lys and GF tended to enhance the effect of GF. Dynamic PET and metabolite analysis by radio-TLC highly revealed that GF blocks the renal reabsorption of (64)Cu-cyclam-RAFT-c(-RGDfK-)4, but does not interfere with its metabolism and excretion. In conclusion, administration of GF and Lys is a useful strategy for kidney protection in (64)Cu-cyclam-RAFT-c(-RGDfK-)4-based internal radiotherapy.
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. Electronic address: zhaohui@nirs.go.jp.
authors: Zhao-Hui
authors: ZH
authors: Jin
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors: Takako
authors: T
authors: Furukawa
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors: Chizuru
authors: C
authors: Sogawa
authors: Département de Chimie Moléculaire, UMR-5250, CNRS-Université Joseph Fourier, Grenoble Cedex 9, France.
authors: Michael
authors: M
authors: Claron
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors: Winn
authors: W
authors: Aung
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors: Atsushi B
authors: AB
authors: Tsuji
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors: Hidekatsu
authors: H
authors: Wakizaka
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors: Ming-Rong
authors: MR
authors: Zhang
authors: Département de Chimie Moléculaire, UMR-5250, CNRS-Université Joseph Fourier, Grenoble Cedex 9, France.
authors: Didier
authors: D
authors: Boturyn
authors: École Nationale Supérieure de Chimie de Montpellier, Montpellier Cedex 5, France.
authors: Pascal
authors: P
authors: Dumy
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors: Yasuhisa
authors: Y
authors: Fujibayashi
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors: Tsuneo
authors: T
authors: Saga
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000378:metabolism*; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D005780:Gelatin / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D008239:Lysine / Q000008:administration & dosage / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010456:Peptides, Cyclic / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D013386:Succinates / Q000008:administration & dosage / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C560405:64Cu-cyclam-RAFT-cyclo(arginyl-glycyl-aspartyl-phenylalanyl-lysyl)4; D056831:Coordination Complexes; D004338:Drug Combinations; D010456:Peptides, Cyclic; D013386:Succinates; C060085:succinylated gelatin; D005780:Gelatin; D008239:Lysine
keywords: (64)Cu labeling; Internal radiotherapy; Multimeric RGD peptide; PET imaging; Renal radioactivity; Succinylated gelatin; l-Lysine