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In Vivo Evaluation of a Self-Excitatory Near-Infrared ImmunoSCIFI Probe

Lookup NU author(s): Dr Katie Gristwood, Dr Saimir LuliORCiD, Dr Helen BlairORCiD, Dr Kenneth RankinORCiD, Dr James KnightORCiD

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Abstract

Secondary Cerenkov-induced Fluorescence Imaging (SCIFI) utilizes blue-weighted Cerenkov luminescence from radioactive decay to excite proximal fluorophores that emit near-infrared light with optimal penetrance through biological tissues, and offers potential utility in clinical imaging applications, including guidance of surgical resection. Recently, we developed a self-excitatory immunoSCIFI probe based on an antibody modified with the Cerenkov luminescence generating radioisotope zirconium-89 and a near-infrared boron-dipyrromethene dye (BOD665) and observed immunoSCIFI signal in in vitro cell-based experiments. In this study, we have evaluated the in vivo application of immunoSCIFI using a clinically relevant orthotopic mouse model of dedifferentiated chondrosarcoma as a reproducible, high contrast setting in which to challenge the optical method under bone and soft tissue attenuation. Herein, we report the synthesis, characterisation, preclinical imaging, and ex vivo biodistribution analysis of a novel immunoSCIFI probe, [⁸⁹Zr]Zr-DFO-MT1-MMP-BOD665, based on a murine monoclonal IgG with high binding specificity for the sarcoma biomarker, MT1-MMP. Both in vivo imaging and ex vivo data indicated significantly higher total uptake and femur-to-muscle ratios in the inoculated femurs with high MT1-MMP expression relative to contralateral femurs. These preliminary findings establish that antibody-mediated SCIFI can operate in vivo with favourable signal-to-background performance under physiologically relevant photon attenuation. The study therefore provides a methodological foundation for future SCIFI probes, for which rigorous specificity testing and broader biomarker panels will be pursued separately.

Publication metadata

Author(s): Gristwood K, Luli S, Blair HJ, Rankin KS, Knight JC

Publication type: Article

Publication status: Published

Journal: Bioconjugate Chemistry

Year: 2026

Volume: 37

Issue: 1

Pages: 93-99

Print publication date: 21/01/2026

Online publication date: 07/01/2026

Acceptance date: 19/12/2025

Date deposited: 06/01/2026

ISSN (print): 1043-1802

ISSN (electronic): 1520-4812

Publisher: American Chemical Society

URL: https://doi.org/10.1021/acs.bioconjchem.5c00506

DOI: 10.1021/acs.bioconjchem.5c00506

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