Radiolabelled 177 Lu-Bispidine-Trastuzumab for Targeting Human Epidermal Growth Factor Receptor 2 Positive Cancers.
Chemistry
; 30(14): e202303805, 2024 Mar 07.
Article
em En
| MEDLINE
| ID: mdl-38064536
ABSTRACT
Radioimmunotherapy (RIT) is a promising alternative to conventional treatment options. Here, we present experimental work on the synthesis, radiochemistry, and inâ
vivo performance of a lanthanoid-selective nonadentate bispidine ligand suitable for 177 Lu3+ ion complexation. The ligand (bisp,1) was derivatised with a photoactivatable aryl azide (ArN3 ) group as a bioconjugation handle for light-induced labelling of proteins. Quantitative radiosynthesis of [177 Lu]Lu-1+ was accomplished in 10 minutes at 40 °C. Subsequent incubation of [177 Lu]Lu-1+ with trastuzumab, followed by irradiation with light at 365â
nm for 15â
min, at room temperature and pHâ
8.0-8.3, gave the radiolabelled mAb, [177 Lu]Lu-1-azepin-trastuzumab ([177 Lu]Lu-1-mAb) in a decay-corrected radiochemical yield of 14 %, and radiochemical purity (RCP)>90 %. Stability studies and cellular binding assays inâ
vitro using the SK-OV-3 human ovarian cancer cells confirmed that [177 Lu]Lu-1-mAb remained biological active and displayed specific binding to HER2/neu. Experiments in immunocompromised female athymic nude mice bearing subcutaneous xenograft models of SK-OV-3 tumours revealed significantly higher tumour uptake in the normal group compared with the control block group (29.8±11.4 %ID g-1 vs. 14.8±6.1 %ID g-1 , respectively; P-value=0.037). The data indicate that bispidine-based ligand systems are suitable starting points for constructing novel, high-denticity chelators for specific complexation of larger radiotheranostic metal ion nuclides.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radioisótopos
/
Receptor ErbB-2
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Compostos Bicíclicos Heterocíclicos com Pontes
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Neoplasias
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Chemistry
Assunto da revista:
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça