Immuno-PET Imaging of TNF-α in Colitis Using 89Zr-DFO-infliximab.
Mol Pharm
; 19(10): 3632-3639, 2022 10 03.
Article
em En
| MEDLINE
| ID: mdl-36039398
ABSTRACT
Tumor necrosis factor-alpha (TNF-α) neutralization has become increasingly important in the treatment of inflammatory bowel diseases (IBD). A series of monoclonal antibodies were approved in the clinic for anti-TNF-α therapy. However, a comprehensive assessment of TNF-α levels throughout the colon, which facilitates the diagnosis of IBD and predicts anti-TNF-α efficacy, remains challenging. Here, we radiolabeled infliximab with long-lived radionuclides 89Zr for immuno-positron emission tomography (PET) imaging of TNF-α in vivo. The increased TNF-α level was detected in the inflammatory colon of the dextran sodium sulfate-induced colitis mice. The immuno-PET imaging of 89Zr-desferrioxamine-infliximab reveals a high uptake (7.1 ± 0.3%ID/g) in the inflammatory colon, which is significantly higher than in the healthy control and blocked groups. The colon-to-muscle ratio reached more than 10 and was maintained at a high level for 10 h after injection. The ex vivo biodistribution study also verified the superior uptake in the inflammatory colon. This study provides an in vivo immune-PET approach to molecular imaging of the pro-inflammatory cytokine TNF-α. It is promising in diagnosing and predicting efficacy in both IBD and other autoimmune diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Inflamatórias Intestinais
/
Colite
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article