Targeted Dual-Modal PET/SPECT-NIR Imaging: From Building Blocks and Construction Strategies to Applications

Abstract

Molecular imaging is an emerging non-invasive method to qualitatively and quantitively visualize and characterize biological processes. Among the imaging modalities, PET/SPECT and near-infrared (NIR) imaging provide synergistic properties that result in deep tissue penetration and up to cell-level resolution. Dual-modal PET/SPECT-NIR agents are commonly combined with a targeting ligand (e.g., antibody or small molecule) to engage biomolecules overexpressed in cancer, thereby enabling selective multimodal visualization of primary and metastatic tumors. The use of such agents for (i) preoperative patient selection and surgical planning and (ii) intraoperative FGS could improve surgical workflow and patient outcomes. However, the development of targeted dual-modal agents is a chemical challenge and a topic of ongoing research. In this review, we define key design considerations of targeted dual-modal imaging from a topological perspective, list targeted dual-modal probes disclosed in the last decade, review recent progress in the field of NIR fluorescent probe development, and highlight future directions in this rapidly developing field.

A Novel PSMA-Targeted Probe for NIRF-Guided Surgery and Photodynamic Therapy: Synthesis and Preclinical Validation

“…In recent years photodynamic therapy (PDT) has been deeply investigated thanks to the availability of new efficient photosensitizers [ 51 , 52 ]. Targeted photodynamic therapy improves the efficacy of the treatment and reduce the toxicity.…”

The Evolution of Fluorescence-Guided Surgery

“…Furthermore, as the field of FGS quickly progresses, various bridges can be made between surgical oncology using fluorescent agents and conventional nuclear imaging using radionuclides. By combining both a fluorescence dye and a radionuclide to targeting agent, a single tracer could be exploited for presurgical nuclear imaging as well as intraoperative fluorescence imaging [ 56 ]. The first in-human example of such dual-modality agent is 68 Ga-NOTA-BBN-IR-800CW which targets gastrin-releasing peptide receptors in glioblastomas [ 57 ].…”

Development of an Immuno-SPECT/Fluorescent Bimodal Tracer Targeting Human or Murine PD-L1 on Preclinical Models

“…In recent years, growing interest in PD-L1 biomarkers has spurred the development of various biomarkers, mainly using immunoagents − or nanoparticles. − At the same time, the exploration of new hybrid imaging agents to make the most of existing imaging methods has grown considerably. − Despite these advances, the field of bimodal imaging of PD-L1 is still in its infancy. Studies on this field have largely revolved around nanoparticles with ferromagnetic properties for MRI imaging. − It is worth noticing that a few studies have focused on the use of small organic probes for bimodal imaging but with the need for repeated injection of probes for each modality. , At present, the development of bimodal organic probes enabling dual imaging in a single injection for PD-L1 imaging remains relatively limited. , …”