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

TL;DR

A new immunoSCIFI probe was tested in mice to detect a sarcoma biomarker using near-infrared light, showing promising in vivo performance.

Contribution

The development and in vivo evaluation of a self-excitatory immunoSCIFI probe for clinical imaging is novel.

Findings

The immunoSCIFI probe showed higher uptake in femurs with high MT1-MMP expression.

Signal-to-background performance was favorable under physiological photon attenuation.

Ex vivo biodistribution confirmed the probe's specificity and contrast in a mouse model.

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
an 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, characterization,
preclinical imaging, and ex vivo biodistribution
analysis of a novel immunoSCIFI probe, [89Zr]­Zr-DFO-MT1-MMP-BOD665,
based on a murine monoclonal immunoglobulin G (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 favorable 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.

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