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European Journal of Nuclear Medicine and Molecular Imaging

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01-08-2021 | Positron Emission Tomography | Original Article

ImmunoPET/NIRF/Cerenkov multimodality imaging of ICAM-1 in pancreatic ductal adenocarcinoma

Authors: Miao Li, Weijun Wei, Todd E. Barnhart, Dawei Jiang, Tianye Cao, Kevin Fan, Jonathan W. Engle, Jianjun Liu, Weiyu Chen, Weibo Cai

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2021

Abstract

Purpose

We dual-labeled an intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody (mAb) and evaluated its effectiveness for lesion detection and surgical navigation in pancreatic ductal adenocarcinoma (PDAC) via multiple noninvasive imaging approaches, including positron emission tomography (PET), near-infrared fluorescence (NIRF), and Cerenkov luminescence imaging (CLI).

Methods

ICAM-1 expression in PDAC cell lines (BxPC-3 and AsPC-1) was assessed via flow cytometry and immunofluorescent staining. An ICAM-1 mAb labeled by IRDye 800CW and radionuclide zirconium-89 (denoted as [⁸⁹Zr]Zr-DFO-ICAM-1-IR800) was synthesized. Its performance was validated via in vivo comparative PET/NIRF/CLI and biodistribution (Bio-D) studies in nude mice bearing subcutaneous BxPC-3/AsPC-1 tumors or orthotopic BxPC-3 tumor models using nonspecific IgG as an isotype control tracer.

Results

ICAM-1 expression was strong in the BxPC-3 and minimal in the AsPC-1 cell line. Both multimodality imaging and Bio-D data exhibited more prominent uptake of [⁸⁹Zr]Zr-DFO-ICAM-1-IR800 in BxPC-3 tumors than in AsPC-1 tumors. The uptake of [⁸⁹Zr]Zr-DFO-IgG-IR800 in BxPC-3 tumors was similar to that of [⁸⁹Zr]Zr-DFO-ICAM-1-IR800 in AsPC-1 tumors. These results demonstrate the desirable affinity and specificity of [⁸⁹Zr]Zr-DFO-ICAM-1-IR800 compared to [⁸⁹Zr]Zr-DFO-IgG-IR800. Orthotopic BxPC-3 tumor foci could also be clearly delineated by [⁸⁹Zr]Zr-DFO-ICAM-1-IR800. An intermodal match was achieved in the ICAM-1–targeted immunoPET/NIRF/CLI. The positive expression levels of ICAM-1 in BxPC-3 tumor tissue were further confirmed by immunohistopathology.

Conclusion

We successfully developed a dual-labeled ICAM-1–targeted tracer for PET/NIRF/CLI of PDAC that can facilitate better diagnosis and intervention of PDAC upon clinical translation.

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Title: ImmunoPET/NIRF/Cerenkov multimodality imaging of ICAM-1 in pancreatic ductal adenocarcinoma
Authors: Miao Li
Weijun Wei
Todd E. Barnhart
Dawei Jiang
Tianye Cao
Kevin Fan
Jonathan W. Engle
Jianjun Liu
Weiyu Chen
Weibo Cai
Publication date: 01-08-2021
Publisher: Springer Berlin Heidelberg
Keyword: Positron Emission Tomography
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2021
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-021-05216-3

At a glance: The STEP trials

Springer Medicine

ImmunoPET/NIRF/Cerenkov multimodality imaging of ICAM-1 in pancreatic ductal adenocarcinoma

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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