Dual-Mode Tumor Imaging Using Probes That Are Responsive to Hypoxia-Induced Pathological Conditions

Abstract

Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality can compensate for the limitations and validate the results of any single imaging modality. In this review, we describe dual-mode imaging systems for the detection of hypoxia that have been reported since the start of the 21st century. First, we provide a brief overview of the hallmarks of hypoxia used for imaging and the imaging modalities used to detect hypoxia, including optical imaging, ultrasound imaging, photoacoustic imaging, single-photon emission tomography, X-ray computed tomography, positron emission tomography, Cerenkov radiation energy transfer imaging, magnetic resonance imaging, electron paramagnetic resonance imaging, magnetic particle imaging, and surface-enhanced Raman spectroscopy, and mass spectrometric imaging. These overviews are followed by examples of hypoxia-relevant imaging using a mixture of probes for complementary single-mode imaging techniques. Then, we describe dual-mode molecular switches that are responsive in multiple imaging modalities to at least one hypoxia-induced pathological change. Finally, we offer future perspectives toward dual-mode imaging of hypoxia and hypoxia-induced pathophysiological changes in tumor microenvironments.

Metal Complexes and Nanoparticles for Photoacoustic Imaging

“…Furthermore, these methods incur substantial investment and operating costs, which render them less suitable for broad screening efforts. [3][4][5] In recent years, an increasing amount of research and development effort has been focused on the investigation of widely applicable, lowcost imaging modalities that are well suited for real-time imaging applications and that pose only minimal health risks to patients. Such techniques notably include ultrasound (US) imaging (USI) and fluorescence imaging (FI) as well as photoacoustic (PA) imaging (PAI), a hybrid technique between USI and FI.…”

In Vivo Biomarker Imaging: Paving the Way for Precision Medicine

“…Pathogen-targeting capabilities can also be achieved using immune cell mimetics. Additionally, several other articles in this Special Issue showcase the in vivo imaging of changes in the extracellular pH [ 3 ], hypoxia [ 4 ], or organ function [ 5 , 6 ] associated with diseases.…”

“…In the meantime, multimodal imaging has become an attractive approach by which complementary imaging methods are utilized, as it provides information that a single method is unable to generate. In the Special Issue, two research papers are specifically focused on multimodal approaches [ 2 , 3 ], while another review paper provides a comprehensive overview of the available dual-mode imaging method, focusing on hypoxia-detection [ 4 ]. Another significant advantage of multimodal approaches is their ability to self-validate and even self-calibrate by utilizing the quantitative information detected by each of the two or more imaging methods.…”

“…Finally, this Special Issue contains three exceptional review articles that encompass the diverse facets of in vivo imaging [ 4 , 8 , 11 ], from real-time cancer stem cell imaging [ 11 ] to quantitative analysis of human CEST MRI data [ 8 ]. Notably, the comprehensive review by Subasinghe and colleagues (spanning 72 pages (main text), 70 figures, and 400 references) provides an in-depth summary of the plethora of studies focused on hypoxia imaging [ 4 ].…”

“…Finally, this Special Issue contains three exceptional review articles that encompass the diverse facets of in vivo imaging [ 4 , 8 , 11 ], from real-time cancer stem cell imaging [ 11 ] to quantitative analysis of human CEST MRI data [ 8 ]. Notably, the comprehensive review by Subasinghe and colleagues (spanning 72 pages (main text), 70 figures, and 400 references) provides an in-depth summary of the plethora of studies focused on hypoxia imaging [ 4 ]. This comprehensive, textbook-like review provides a brief introduction to the hallmarks of hypoxia, together with an extensive overview of the various imaging modalities utilized to detect hypoxia; this is, indeed, is invaluable for readers interested in hypoxia imaging.…”