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Lookup NU author(s): Katie Gristwood, Dr Saimir LuliORCiD, Dr Kenneth RankinORCiD, Dr James KnightORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Secondary Cerenkov-induced fluorescence imaging (SCIFI) is an emerging biomedical optical imaging modality that leverages Cerenkov luminescence, primarily generated by β-emitting radioisotopes, to excite fluorophores that offer near-infrared emissions with optimal tissue penetrance. Dual-functionalized immunoconjugates composed of an antibody, a near-infrared fluorophore, and a β-emitting radioisotope have potential utility as novel SCIFI constructs with high specificity for molecular biomarkers of disease. Here, we report the synthesis and characterization of [89Zr]Zr-DFO-trastuzumab-BOD665, a self-excitatory HER2-specific “immunoSCIFI” probe capable of yielding near-infrared fluorescence in situ without external excitation. The penetration depth of the SCIFI signal was measured in hemoglobin-infused optical tissue phantoms that indicated a 2.05-fold increase compared to 89Zr-generated Cerenkov luminescence. Additionally, the binding specificity of the immunoSCIFI probe for HER2 was evaluated in a cellular assay that showed significantly higher binding to SKBR3 (high HER2 expression) relative to MDA-MB-468 (low HER2) breast cancer cells based on measurements of total flux in the near-infrared region with external excitation blocked. Taken together, the results of this study indicate the potential utility of immunoSCIFI constructs for interrogation of molecular biomarkers of disease.
Author(s): Gristwood K, Luli S, Rankin KS, Knight JC
Publication type: Article
Publication status: Published
Journal: ACS Omega
Year: 2023
Volume: 8
Issue: 50
Pages: 47905-47912
Online publication date: 07/12/2023
Acceptance date: 20/11/2023
Date deposited: 18/12/2023
ISSN (electronic): 2470-1343
Publisher: American Chemical Society
URL: https://doi.org/10.1021/acsomega.3c06452
DOI: 10.1021/acsomega.3c06452
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