Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT.
| Autor: | Alakonya H; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Koustoulidou S; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Hopkins SL; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Veal M; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Ajenjo J; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Sneddon D; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.; Department of Chemistry, University of Oxford, Oxford, United Kingdom., Dias G; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Mosley M; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Baguña Torres J; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Amoroso F; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Anderson A; Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; and., Banham AH; Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; and., Cornelissen B; Department of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom; bart.cornelissen@oncology.ox.ac.uk.; Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2024 Oct 01; Vol. 65 (10), pp. 1626-1632. Date of Electronic Publication: 2024 Oct 01. |
| DOI: | 10.2967/jnumed.124.267736 |
| Abstrakt: | 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 111 In to allow SPECT imaging. 111 In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non-p53-specific 111 In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells. Results: In vivo SPECT imaging showed enhanced uptake of 111 In-anti-p53-TAT, versus 111 In-mIgG-TAT, in high-expression p53 R175H 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 111 In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53 R172H 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. (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|