Multi-modal imaging of high-risk ductal carcinoma in situ of the breast using C2Am: a targeted cell death imaging agent.
Animals
Breast Neoplasms
/ diagnostic imaging
Carcinoma in Situ
/ diagnostic imaging
Carcinoma, Ductal, Breast
/ diagnostic imaging
Cell Death
Cell Line, Tumor
Contrast Media
Disease Models, Animal
Early Detection of Cancer
Female
Humans
Immunohistochemistry
Mice
Molecular Imaging
Multimodal Imaging
/ methods
Optical Imaging
Photoacoustic Techniques
DCIS
Early detection
Multi-modal imaging
Necrosis
Optoacoustic
Journal
Breast cancer research : BCR
ISSN: 1465-542X
Titre abrégé: Breast Cancer Res
Pays: England
ID NLM: 100927353
Informations de publication
Date de publication:
17 02 2021
17 02 2021
Historique:
received:
15
10
2020
accepted:
01
02
2021
entrez:
18
2
2021
pubmed:
19
2
2021
medline:
7
1
2022
Statut:
epublish
Résumé
Ductal carcinoma in situ (DCIS) is a non-invasive form of early breast cancer, with a poorly understood natural history of invasive transformation. Necrosis is a well-recognized adverse prognostic feature of DCIS, and non-invasive detection of its presence and spatial extent could provide information not obtainable by biopsy. We describe here imaging of the distribution and extent of comedo-type necrosis in a model of human DCIS using C2Am, an imaging agent that binds to the phosphatidylserine exposed by necrotic cells. We used an established xenograft model of human DCIS that mimics the histopathological features of the disease. Planar near-infrared and optoacoustic imaging, using fluorescently labeled C2Am, were used to image non-invasively the presence and extent of lesion necrosis. C2Am showed specific and sensitive binding to necrotic areas in DCIS tissue, detectable both in vivo and ex vivo. The imaging signal generated in vivo using near-infrared (NIR) fluorescence imaging was up to 6-fold higher in DCIS lesions than in surrounding fat pad or skin tissue. There was a correlation between the C2Am NIR fluorescence (Pearson R = 0.783, P = 0.0125) and optoacoustic signals (R > 0.875, P < 0.022) in the DCIS lesions in vivo and the corresponding levels of cell death detected histologically. C2Am is a targeted multi-modal imaging agent that could complement current anatomical imaging methods for detecting DCIS. Imaging the presence and spatial extent of necrosis may give better prognostic information than that obtained by biopsy alone.
Sections du résumé
BACKGROUND
Ductal carcinoma in situ (DCIS) is a non-invasive form of early breast cancer, with a poorly understood natural history of invasive transformation. Necrosis is a well-recognized adverse prognostic feature of DCIS, and non-invasive detection of its presence and spatial extent could provide information not obtainable by biopsy. We describe here imaging of the distribution and extent of comedo-type necrosis in a model of human DCIS using C2Am, an imaging agent that binds to the phosphatidylserine exposed by necrotic cells.
METHODS
We used an established xenograft model of human DCIS that mimics the histopathological features of the disease. Planar near-infrared and optoacoustic imaging, using fluorescently labeled C2Am, were used to image non-invasively the presence and extent of lesion necrosis.
RESULTS
C2Am showed specific and sensitive binding to necrotic areas in DCIS tissue, detectable both in vivo and ex vivo. The imaging signal generated in vivo using near-infrared (NIR) fluorescence imaging was up to 6-fold higher in DCIS lesions than in surrounding fat pad or skin tissue. There was a correlation between the C2Am NIR fluorescence (Pearson R = 0.783, P = 0.0125) and optoacoustic signals (R > 0.875, P < 0.022) in the DCIS lesions in vivo and the corresponding levels of cell death detected histologically.
CONCLUSIONS
C2Am is a targeted multi-modal imaging agent that could complement current anatomical imaging methods for detecting DCIS. Imaging the presence and spatial extent of necrosis may give better prognostic information than that obtained by biopsy alone.
Identifiants
pubmed: 33596961
doi: 10.1186/s13058-021-01404-z
pii: 10.1186/s13058-021-01404-z
pmc: PMC7891030
doi:
Substances chimiques
Contrast Media
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
25Subventions
Organisme : Cancer Research UK
ID : 17242
Pays : United Kingdom
Organisme : Cancer Research UK EPSRC
ID : 16465
Commentaires et corrections
Type : ErratumIn
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