NIR fluorescence imaging and treatment for cancer immunotherapy

Abstract

Cancer immunotherapy has emerged as one of the most powerful anticancer therapies. However, the details on the interaction between tumors and the immune system are complicated and still poorly understood. Optical fluorescence imaging is a technique that allows for the visualization of fluorescence-labeled immune cells and monitoring of the immune response during immunotherapy. To this end, near-infrared (NIR) light has been adapted for optical fluorescence imaging because it is relatively safe and simple without hazardous ionizing radiation and has relatively deeper tissue penetration into living organisms than visible fluorescence light. In this review, we discuss state-of-the-art NIR optical imaging techniques in cancer immunotherapy to observe the dynamics, efficacy, and responses of the immune components in living organisms. The use of bioimaging labeling techniques will give us an understanding of how the immune system is primed and ultimately developed.

Skin Cancer Pathobiology at a Glance: A Focus on Imaging Techniques and Their Potential for Improved Diagnosis and Surveillance in Clinical Cohorts

“…Although NIR fluorescence imaging seems to be the ideal tool for the observation of immune components in a real-time setting, the selection of the right fluorophores is a key step in this process, as the physicochemical properties of labeling agents (e.g., molecular weight (MW), absorption/emission wavelengths, surface charges, hydrodynamic diameter (HD), pKa, photostability, hydrophobicity, and plasma protein binding) may greatly impact their optical performance. The ideal imaging probe for labeling the immune components of interest should have the following essential properties: high imaging affinity and specificity for the desired immune components, acceptable safety profiles, and minimal immunogenic toxicity [ 193 ]. The labeling tools that are currently available for marking immune cells in the NIR window include small-molecule fluorophores (cyanines, phthalocyanines, porphyrin derivatives, squaraine derivatives, and BODIPY analogs), nanoparticles (nanocrystals, QDs, and metal nanoshells), and targeted (antibodies, peptides, and protein complex probes) and activatable probes [ 185 ].…”

“…The labeling tools that are currently available for marking immune cells in the NIR window include small-molecule fluorophores (cyanines, phthalocyanines, porphyrin derivatives, squaraine derivatives, and BODIPY analogs), nanoparticles (nanocrystals, QDs, and metal nanoshells), and targeted (antibodies, peptides, and protein complex probes) and activatable probes [ 185 ]. Activatable probes encompass in essence the same compounds as targeted probes, but their fluorescence can be quantitated in response to internal microenvironment stimuli such as pH, enzymes, and oxidative stress [ 193 ]. NIR probes may be applied both in vivo and ex vivo for monitoring the behavior of immune components.…”

“…Notably, ex vivo labeling is not restricted to effector immune cells and may be applicable to any type of immunological agents, including vaccines [ 194 ]. This method is frequently used for T-cell tracking in the context of cancer immunotherapy or Chimeric antigen receptor (CAR) T-cell therapy in preclinical models [ 193 , 195 ]. There are, however, significant limitations to the ex vivo method as the isolation and labeling procedures may affect the viability of lymphocytes.…”

“…Therefore, a new methodology is highly desired to indirectly label sensitive immune cells such as T and B cells in vivo with exogenously administered fluorophores [ 185 ]. Currently, the scientific efforts for in vivo NIR imaging are focused on using specific fluorophores that can target particular surface receptors or membrane transporters of cells and on employing activatable fluorophores for monitoring and assessing the complexity of the immune responses in living organisms [ 193 ]. Several authors exploited the potential of peptide substrate that are responsive to granzyme B (GranB) for the in vivo evaluation of immunotherapy.…”

Ultrabright Renal-Clearable Cyanine-Protein Nanoprobes for High-Quality NIR-II Angiography and Lymphography

“…Near-infrared (NIR) imaging has had a substantial impact on clinical diagnosis and navigation surgery. − The improved photon transport from visible light to NIR light facilitates the imaging penetration depth from micrometer to millimeter or even centimeter. , Fluorescence imaging has ushered in a new-generation NIR imaging window from 900 to 2000 nm (NIR-II, also defined as shortwave infrared), with much-improved penetration depth and imaging contrast. − To date, only several NIR fluorophores, such as indocyanine green (ICG), IRDye800CW, and ZW800-1, are undergoing clinical applications or clinical trials. − Recently, a series of cyanine dyes with bright emission tails in the NIR-II window were found when spectroscopically characterized on indium gallium arsenide (InGaAs) detectors. − Thus, repurposing NIR-I peak dyes will directly impact imaging outcomes in various biological events including perfusion imaging, sentinel lymph node mapping, and molecular cancer imaging. Nevertheless, currently used cyanine dyes suffer from rapid photobleaching, low NIR-II brightness, and uncontrollable pharmacokinetics, hampering their biological identification applications. − …”