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Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Affinity-Guided Conjugation to Antibodies for Use in Positron Emission Tomography

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  1. Oxime Coupling of Active Site Inhibited Factor Seven with a Nonvolatile, Water-Soluble Fluorine-18 Labeled Aldehyde

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  2. Molecular Targeted NIR-II Probe for Image-Guided Brain Tumor Surgery

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  3. Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer

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  4. Synthesis and Evaluation of Astatinated N-[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates

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  1. Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis

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  2. Limited diagnostic utility of Chromogranin A measurements in workup of neuroendocrine tumors

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  3. Blocking of efflux transporters in rats improves translational validation of brain radioligands

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  4. Renal 123I-MIBG Uptake before and after Live-Donor Kidney Transplantation

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Vis graf over relationer

The radionuclide copper-64 is widely used in combination with biomolecules, such as antibodies, for positron emission tomography (PET). Copper-64 is ideal for the imaging of biomolecules with long circulation times due to its relatively long half-life, and when conjugated to an antibody, specific cells can be targeted in vivo. Here, we have prepared a trastuzumab-chelator conjugate by using affinity-guided conjugation, in which an azide was attached to the antibody prior to a strain promoted azide-alkyne cycloaddition reaction with DBCO-PEG4-NOTA. The conjugate was benchmarked against a standard nonspecific labeled trastuzumab-NOTA conjugate. The conjugates were tested for incorporation of copper-64, stability in buffer and plasma, and tumor targeting in vivo using PET imaging of mice with xenograft tumors expressing HER2. Both conjugates showed good incorporation of copper-64 and a high stability with less than 10% degradation after 36 h. Furthermore, both conjugates showed accumulation at the tumor site with mean uptake of 7.2 ± 2.4%ID/g and 5.2 ± 1.3%ID/g after 40 h for the affinity-guided labeled trastuzumab and the nonspecific labeled trastuzumab, respectively.

OriginalsprogEngelsk
TidsskriftBioconjugate Chemistry
Vol/bind30
Udgave nummer3
Sider (fra-til)881-887
Antal sider7
ISSN1043-1802
DOI
StatusUdgivet - 20 mar. 2019

ID: 59322615