Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT.
J Nucl Med
; 65(10): 1626-1632, 2024 Oct 01.
Article
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| MEDLINE
| ID: mdl-39266290
ABSTRACT
Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first-to our knowledge-method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer. Methods:
Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with 111In to allow SPECT imaging. 111In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non-p53-specific 111In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells.Results:
In vivo SPECT imaging showed enhanced uptake of 111In-anti-p53-TAT, versus 111In-mIgG-TAT, in high-expression p53R175H and medium-expression wild-type p53 but not in null p53 tumor xenografts. The results were confirmed in mice bearing genetically engineered KPC mouse-derived pancreatic ductal adenocarcinoma tumors. Imaging with 111In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53R172H pancreatic ductal adenocarcinoma tumors.Conclusion:
We demonstrate the feasibility of noninvasive in vivo molecular imaging of p53 in tumor tissue using a radiolabeled TAT-modified monoclonal antibody.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tomografía Computarizada de Emisión de Fotón Único
/
Proteína p53 Supresora de Tumor
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Nucl Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido
Pais de publicación:
Estados Unidos