Preclinical evaluation of anti-VEGFR2 monoclonal antibody ramucirumab labelled with zirconium-89 for tumour imaging
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
33818828
DOI
10.1002/jlcr.3909
Knihovny.cz E-zdroje
- Klíčová slova
- PET, VEGF, VEGFR, angiogenesis, monoclonal antibody, ramucirumab,
- MeSH
- humanizované monoklonální protilátky * chemie terapeutické užití farmakokinetika MeSH
- izotopové značení MeSH
- lidé MeSH
- monoklonální protilátky * chemie farmakokinetika MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- PET/CT metody MeSH
- radionuklidy * chemie MeSH
- ramucirumab * MeSH
- receptor 2 pro vaskulární endoteliální růstový faktor * metabolismus antagonisté a inhibitory MeSH
- tkáňová distribuce MeSH
- zirkonium * chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- humanizované monoklonální protilátky * MeSH
- monoklonální protilátky * MeSH
- radionuklidy * MeSH
- ramucirumab * MeSH
- receptor 2 pro vaskulární endoteliální růstový faktor * MeSH
- Zirconium-89 MeSH Prohlížeč
- zirkonium * MeSH
The key factors participating in angiogenesis include vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), particularly VEGFR2. Angiogenesis suppression comprises the blocking of the VEGFR2 binding site by the monoclonal antibody ramucirumab (RAM). Our study focused on RAM radiolabelling with zirconium-89 along with subsequent in vitro and in vivo biological evaluation. RAM was conjugated with the bifunctional chelator p-SCN-Bn-deferoxamine (DFO) and subsequently radiolabelled with [89 Zr]Zr-oxalate. The binding affinity of [89 Zr]Zr-DFO-RAM to VEGFR2 was tested in vitro on prostate (PC-3) and ovary adenocarcinoma (SK-OV-3) cell lines. The positron emission tomography/computed tomography (PET/CT) imaging and ex vivo biodistribution experiments were performed in PC-3 and SK-OV-3 xenografted mice. The in vitro experiments revealed the preserved binding affinity of [89 Zr]Zr-DFO-RAM to VEGFR2. The obtained ex vivo biodistribution data showed the uptake in PC-3 and SK-OV-3 tumours at about 8.7 ± 0.2 and 12.1 ± 1.6%ID/g, respectively. The tumour-to-muscle ratio for 1, 3 and 6 days post injection was 3.9, 5.5 and 5.12 for PC-3 and 6.0, 8.0 and 8.82 for SK-OV-3 tumours, respectively. PET/CT images showed high radioactivity accumulation in the tumours starting already on the first day after tracer administration. The obtained results proved the potency of [89 Zr]Zr-DFO-RAM to target and image VEGFR2-positive tumours in vivo.
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