Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer
Colorectal cancer (CRC) is the third most common malignancy in the world, with 22% of patients presenting with metastatic disease and a further 50% destined to develop metastasis. Molecular imaging uses antigen-specific ligands conjugated to radionuclides to detect and characterise primary cancer an...
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2021-01-01
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Series: | Contrast Media & Molecular Imaging |
Online Access: | http://dx.doi.org/10.1155/2021/3153278 |
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doaj-12ffab03d4ea4168b652ca01e706bfaf2021-09-27T00:51:42ZengHindawi-WileyContrast Media & Molecular Imaging1555-43172021-01-01202110.1155/2021/3153278Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal CancerTahleesa J. Cuda0Yaowu He1Thomas Kryza2Tashbib Khan3Brian W. Tse4Kamil A. Sokolowski5Cheng Liu6Nicholas Lyons7Madeline Gough8Cameron E. Snell9David K. Wyld10Stephen Rose11Andrew D. Riddell12Andrew R. L. Stevenson13Paul A. Thomas14David A. Clark15Simon Puttick16John D. Hooper17Faculty of MedicineMater Research Institute The University of QueenslandMater Research Institute The University of QueenslandMater Research Institute The University of QueenslandPreclinical Imaging Core FacilityPreclinical Imaging Core FacilityFaculty of MedicineFaculty of MedicineMater Research Institute The University of QueenslandMater Research Institute The University of QueenslandFaculty of MedicineCommonwealth Scientific and Industrial Research OrganisationRedcliffe HospitalFaculty of MedicineFaculty of MedicineFaculty of MedicineCommonwealth Scientific and Industrial Research OrganisationMater Research Institute The University of QueenslandColorectal cancer (CRC) is the third most common malignancy in the world, with 22% of patients presenting with metastatic disease and a further 50% destined to develop metastasis. Molecular imaging uses antigen-specific ligands conjugated to radionuclides to detect and characterise primary cancer and metastases. Expression of the cell surface protein CDCP1 is increased in CRC, and here we sought to assess whether it is a suitable molecular imaging target for the detection of this cancer. CDCP1 expression was assessed in CRC cell lines and a patient-derived xenograft to identify models suitable for evaluation of radio-labelled 10D7, a CDCP1-targeted, high-affinity monoclonal antibody, for preclinical molecular imaging. Positron emission tomography-computed tomography was used to compare zirconium-89 (89Zr)-10D7 avidity to a nonspecific, isotype control 89Zr-labelled IgGκ1 antibody. The specificity of CDCP1-avidity was further confirmed using CDCP1 silencing and blocking models. Our data indicate high avidity and specificity for of 89Zr-10D7 in CDCP1 expressing tumors at. Significantly higher levels than normal organs and blood, with greatest tumor avidity observed at late imaging time points. Furthermore, relatively high avidity is detected in high CDCP1 expressing tumors, with reduced avidity where CDCP1 expression was knocked down or blocked. The study supports CDCP1 as a molecular imaging target for CRC in preclinical PET-CT models using the radioligand 89Zr-10D7.http://dx.doi.org/10.1155/2021/3153278 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tahleesa J. Cuda Yaowu He Thomas Kryza Tashbib Khan Brian W. Tse Kamil A. Sokolowski Cheng Liu Nicholas Lyons Madeline Gough Cameron E. Snell David K. Wyld Stephen Rose Andrew D. Riddell Andrew R. L. Stevenson Paul A. Thomas David A. Clark Simon Puttick John D. Hooper |
spellingShingle |
Tahleesa J. Cuda Yaowu He Thomas Kryza Tashbib Khan Brian W. Tse Kamil A. Sokolowski Cheng Liu Nicholas Lyons Madeline Gough Cameron E. Snell David K. Wyld Stephen Rose Andrew D. Riddell Andrew R. L. Stevenson Paul A. Thomas David A. Clark Simon Puttick John D. Hooper Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer Contrast Media & Molecular Imaging |
author_facet |
Tahleesa J. Cuda Yaowu He Thomas Kryza Tashbib Khan Brian W. Tse Kamil A. Sokolowski Cheng Liu Nicholas Lyons Madeline Gough Cameron E. Snell David K. Wyld Stephen Rose Andrew D. Riddell Andrew R. L. Stevenson Paul A. Thomas David A. Clark Simon Puttick John D. Hooper |
author_sort |
Tahleesa J. Cuda |
title |
Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer |
title_short |
Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer |
title_full |
Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer |
title_fullStr |
Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer |
title_full_unstemmed |
Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer |
title_sort |
preclinical molecular pet-ct imaging targeting cdcp1 in colorectal cancer |
publisher |
Hindawi-Wiley |
series |
Contrast Media & Molecular Imaging |
issn |
1555-4317 |
publishDate |
2021-01-01 |
description |
Colorectal cancer (CRC) is the third most common malignancy in the world, with 22% of patients presenting with metastatic disease and a further 50% destined to develop metastasis. Molecular imaging uses antigen-specific ligands conjugated to radionuclides to detect and characterise primary cancer and metastases. Expression of the cell surface protein CDCP1 is increased in CRC, and here we sought to assess whether it is a suitable molecular imaging target for the detection of this cancer. CDCP1 expression was assessed in CRC cell lines and a patient-derived xenograft to identify models suitable for evaluation of radio-labelled 10D7, a CDCP1-targeted, high-affinity monoclonal antibody, for preclinical molecular imaging. Positron emission tomography-computed tomography was used to compare zirconium-89 (89Zr)-10D7 avidity to a nonspecific, isotype control 89Zr-labelled IgGκ1 antibody. The specificity of CDCP1-avidity was further confirmed using CDCP1 silencing and blocking models. Our data indicate high avidity and specificity for of 89Zr-10D7 in CDCP1 expressing tumors at. Significantly higher levels than normal organs and blood, with greatest tumor avidity observed at late imaging time points. Furthermore, relatively high avidity is detected in high CDCP1 expressing tumors, with reduced avidity where CDCP1 expression was knocked down or blocked. The study supports CDCP1 as a molecular imaging target for CRC in preclinical PET-CT models using the radioligand 89Zr-10D7. |
url |
http://dx.doi.org/10.1155/2021/3153278 |
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