Paradigms in Fluorescence Molecular Imaging: Maximizing Measurement of Biological Changes in Disease, Therapeutic Efficacy, and Toxicology/Safety

Abstract

Fluorescence molecular imaging (MI) is an important concept in preclinical research that focuses on the visualization of cellular and biological function in a non-invasive fashion to better understand in vivo disease processes and treatment effects. MI differs fundamentally from traditional preclinical imaging strategies in that it generally relies on reporter probes specific for particular targets or pathways that can be used to reveal biological changes in situ, at the site(s) of disease. In contrast, the more established imaging modalities, like magnetic resonance imaging, X-ray, micro X-ray computed tomography, and ultrasound, historically have relied primarily on late-stage anatomical or physiologic changes. The practical application of fluorescence MI, however, has drifted somewhat from the emphasis on quantifying biology, and based on the publication record, it now appears to include any imaging in which a probe or contrast agent is used to non-invasively acquire in vivo endpoint information. Unfortunately, the mere use of a defined biologically specific probe, in the absence of careful study design, does not guarantee that any useful biological information is actually gained, although often useful endpoint results still can be achieved. This review proposes to add subcategories of MI, termed MI biological assessment (or MIBA), that emphasize a focus on obtaining early and clear biological changes associated with disease development, therapeutic efficacy, and drug-induced tissue changes. Proper selection of probes and careful study design are critical for maximizing the non-invasive assessment of in vivo biological changes, and applications of these critical elements are described.

Near-Infrared Fluorescent Probes as Imaging and Theranostic Modalities for Amyloid-Beta and Tau Aggregates in Alzheimer’s Disease

“…Moreover, several such molecules are under investigation as theranostic for early diagnosis and as therapeutic agents for AD, which we will address later in section . In addition, recent advances in fluorescence molecular tomography (FMT) and algorithms for simulating light propagation through tissue facilitated 3D fluorescence imaging in the living object, which further strengthen the clinical application of fluorescence imaging. − Therefore, optical imaging probes have emerged as a powerful tool in modern neuroscience due to their rapid evolution and broad pharmacological pre-clinical utility for in vitro and in vivo detection of AD biomarkers (Figure B). − In Table , a brief overview and clinical significance of several applicable AD diagnostic techniques are presented.…”

Fluorescent Reporters for Drug Delivery Monitoring

“…The fluorescent reporters bound to both types of therapeutic agents, drugs and Drug‐Carrier conjugates, enable fluorescence monitoring of drug delivery. Fluorescent TDD monitoring is mostly associated with theranostics (a combination of diagnostics and therapy), cancer treatment, personalized medicine, and pharmaceutical research …”

“…Fluorescent TDD monitoring is mostly associated with theranostics (a combination of diagnostics and therapy), [25] cancer treatment, [26] personalized medicine, [22e,27] and pharmaceutical research. [10b, 28,29] Fluorescent DD/TDD systems can be monitored in vitro and in vivo by using fluorescence imaging and spectroscopy. [17b,30] It is worth mentioning that drug delivery can also be tracked by several other non-invasive techniques such as magnetic resonance imaging, [31] ultrasound imaging, [32] or electrochemical measurements.…”