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Site-Specific 64Cu Labeling of the Serine Protease, Active Site Inhibited Factor Seven Azide (FVIIai-N3), Using Copper Free Click Chemistry.
Jeppesen, Troels E; Kristensen, Lotte K; Nielsen, Carsten H; Petersen, Lars C; Kristensen, Jesper B; Behrens, Carsten; Madsen, Jacob; Kjaer, Andreas.
Afiliação
  • Jeppesen TE; Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen , Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
  • Kristensen LK; Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen , Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
  • Nielsen CH; Minerva Imaging ApS , Ole Maaløes Vej 3, DK-2200 Copenhagen N, Denmark.
  • Petersen LC; Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen , Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
  • Kristensen JB; Minerva Imaging ApS , Ole Maaløes Vej 3, DK-2200 Copenhagen N, Denmark.
  • Behrens C; Novo Nordisk A/S , Novo Allé, DK-2880 Bagsvaerd, Denmark.
  • Madsen J; Novo Nordisk A/S , Novo Allé, DK-2880 Bagsvaerd, Denmark.
  • Kjaer A; Novo Nordisk A/S , Novo Allé, DK-2880 Bagsvaerd, Denmark.
Bioconjug Chem ; 29(1): 117-125, 2018 01 17.
Article em En | MEDLINE | ID: mdl-29206443
ABSTRACT
A method for site-specific radiolabeling of the serine protease active site inhibited factor seven (FVIIai) with 64Cu has been applied using a biorthogonal click reaction. FVIIai binds to tissue factor (TF), a trans-membrane protein involved in hemostasis, angiogenesis, proliferation, cell migration, and survival of cancer cells. First a single azide moiety was introduced in the active site of this 50 kDa protease. Then a NOTA moiety was introduced via a strain promoted azide-alkyne reaction and the corresponding conjugate was labeled with 64Cu. Binding to TF and the stability was evaluated in vitro. TF targeting capability of the radiolabeled conjugate was tested in vivo by positron emission tomography (PET) imaging in pancreatic human xenograft cancer mouse models with various TF expressions. The conjugate showed good stability (>91% at 16 h), an immunoreactivity of 93.5%, and a mean tumor uptake of 2.1 ± 0.2%ID/g at 15 h post injection. In conclusion, FVIIai was radiolabeled with 64Cu in single well-defined position of the protein. This method can be utilized to prepare conjugates from serine proteases with the label at a specific position.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Azidas / Fator VII / Tromboplastina / Radioisótopos de Cobre / Serina Proteases / Química Click Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Bioconjug Chem Assunto da revista: BIOQUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Dinamarca

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Azidas / Fator VII / Tromboplastina / Radioisótopos de Cobre / Serina Proteases / Química Click Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Bioconjug Chem Assunto da revista: BIOQUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Dinamarca