title: Investigation of a potential scintigraphic tracer for imaging apoptosis: radioiodinated annexin V-Kunitz protease inhibitor fusion protein.
abstract: Radiolabeled annexin V (ANV) has been widely used for imaging cell apoptosis. Recently, a novel ANV-Kunitz-type protease inhibitor fusion protein, ANV-6L15, was found to be a promising probe for improved apoptosis detection based on its higher affinity to phosphatidylserine (PS) compared to native ANV. The present paper investigates the feasibility of apoptosis detection using radioiodinated ANV-6L15. Native ANV and ANV-6L15 were labeled with iodine-123 and iodine-125 using Iodogen method. The binding between the radioiodinated proteins and erythrocyte ghosts or chemical-induced apoptotic cells was examined. ANV-6L15 can be radioiodinated with high yield (40%-60%) and excellent radiochemical purity (>95%). (123)I-ANV-6L15 exhibited a higher binding ratio to erythrocyte ghosts and apoptotic cells compared to (123)I-ANV. The biodistribution of (123)I-ANV-6L15 in mice was also characterized. (123)I-ANV-6L15 was rapidly cleared from the blood. High uptake in the liver and the kidneys may limit the evaluation of apoptosis in abdominal regions. Our data suggest that radiolabeled ANV-6L15 may be a better scintigraphic tracer than native ANV for apoptosis detection.
authors.affiliation: Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Mei-Hsiu
authors.initials: MH
authors.lastname: Liao
authors.forename: Tong-Rong
authors.initials: TR
authors.lastname: Jan
authors.forename: Chao-Chih
authors.initials: CC
authors.lastname: Chiang
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Yen
authors.forename: Tse-Zung
authors.initials: TZ
authors.lastname: Liao
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Chen
authors.forename: Chin-Wen
authors.initials: CW
authors.lastname: Chi
authors.forename: Tze-Chein
authors.initials: TC
authors.lastname: Wun
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Shiaw-Pyng
authors.initials: SP
authors.lastname: Wey
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000737:chemistry* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000502:physiology*; D007611:Aprotinin / Q000737:chemistry* / Q000493:pharmacokinetics; D004910:Erythrocyte Membrane / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007457:Iodine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D051598:Whole Body Imaging
chemical_list: D017304:Annexin A5; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; D007611:Aprotinin