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Clinical and Translational Medicine Mar 2021
Topics: Diagnostic Imaging; Humans; Molecular Imaging; Molecular Medicine; Spatio-Temporal Analysis
PubMed: 33784006
DOI: 10.1002/ctm2.347 -
Nanotheranostics 2022'See what you treat and treat what you see, at a molecular level', could be the motto of theranostics. The concept implies diagnosis (imaging) and treatment of cells... (Review)
Review
'See what you treat and treat what you see, at a molecular level', could be the motto of theranostics. The concept implies diagnosis (imaging) and treatment of cells (usually cancer) using the same molecule, thus guaranteeing a targeted cytotoxic approach of the imaged tumor cells while sparing healthy tissues. As the brilliant late Sam Gambhir would say, the imaging agent acts like a 'molecular spy' and reveals where the tumoral cells are located and the extent of disease burden (diagnosis). For treatment, the same 'molecular spy' docks to the same tumor cells, this time delivering cytotoxic doses of radiation (treatment). This duality represents the concept of a 'theranostic pair', which follows the scope and fundamental principles of targeted precision and personalized medicine. Although the term was noted in medical literature in the early 2000s, the principle is not at all new to nuclear medicine. The first example of theranostic dates back to 1941 when Dr. Saul Hertz first applied radioiodine for radionuclide treatment of thyroid cells in patients with hyperthyroidism. Ever since, theranostics has been an integral element of nuclear medicine and molecular imaging. The more we understand tumor biology and molecular pathology of carcinogenesis, including specific mutations and receptor expression profiles, the more specific these 'molecular spies' can be developed for diagnostic molecular imaging and subsequent radionuclide targeted therapy (radiotheranostics). The appropriate selection of the diagnostic and therapeutic radionuclide for the 'theranostic pair' is critical and takes into account not only the type of cytotoxic radiation emission, but also the linear energy transfer (LET), and the physical half-lives. Advances in radiochemistry and radiopharmacy with new radiolabeling techniques and chelators are revolutionizing the field. The landscape of cytotoxic systemic radionuclide treatments has dramatically expanded through the past decades thanks to all these advancements. This article discusses present and promising future theranostic applications for various types of diseases such as thyroid disorders, neuroendocrine tumors (NET), pediatric malignancies, and prostate cancer (PC), and provides an outlook for future perspectives.
Topics: Child; Humans; Iodine Radioisotopes; Male; Molecular Imaging; Neuroendocrine Tumors; Nuclear Medicine; Precision Medicine; Theranostic Nanomedicine
PubMed: 34976584
DOI: 10.7150/ntno.64141 -
American Journal of Respiratory and... Jan 2021
Topics: Humans; Idiopathic Pulmonary Fibrosis; Molecular Imaging; Receptors, Chemokine
PubMed: 32791001
DOI: 10.1164/rccm.202007-2897ED -
Nature Communications Feb 2023To date, a biopsy is mandatory to evaluate parenchymal inflammation in the liver. Here, we evaluated whether molecular imaging of vascular cell adhesion molecule-1...
To date, a biopsy is mandatory to evaluate parenchymal inflammation in the liver. Here, we evaluated whether molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) could be used as an alternative non-invasive tool to detect liver inflammation in the setting of chronic liver disease. To do so, we radiolabeled anti-VCAM-1 nanobody (Tc-cAbVCAM1-5) and used single-photon emission computed tomography (SPECT) to quantify liver uptake in preclinical models of non-alcoholic fatty liver disease (NAFLD) with various degree of liver inflammation: wild-type mice fed a normal or high-fat diet (HFD), FOZ fed a HFD and C57BL6/J fed a choline-deficient or -supplemented HFD. Tc-cAbVCAM1-5 uptake strongly correlates with liver histological inflammatory score and with molecular inflammatory markers. The diagnostic power to detect any degree of liver inflammation is excellent (AUROC 0.85-0.99). These data build the rationale to investigate Tc-cAbVCAM1-5 imaging to detect liver inflammation in patients with NAFLD, a largely unmet medical need.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Vascular Cell Adhesion Molecule-1; Liver; Hepatitis; Inflammation; Molecular Imaging; Diet, High-Fat; Mice, Inbred C57BL
PubMed: 36828835
DOI: 10.1038/s41467-023-36776-7 -
Journal of Biomedical Optics Jan 2021Deep-tissue penetration by x-rays to induce optical responses of specific molecular reporters is a new way to sense and image features of tissue function in vivo.... (Review)
Review
SIGNIFICANCE
Deep-tissue penetration by x-rays to induce optical responses of specific molecular reporters is a new way to sense and image features of tissue function in vivo. Advances in this field are emerging, as biocompatible probes are invented along with innovations in how to optimally utilize x-ray sources.
AIM
A comprehensive review is provided of the many tools and techniques developed for x-ray-induced optical molecular sensing, covering topics ranging from foundations of x-ray fluorescence imaging and x-ray tomography to the adaptation of these methods for sensing and imaging in vivo.
APPROACH
The ways in which x-rays can interact with molecules and lead to their optical luminescence are reviewed, including temporal methods based on gated acquisition and multipoint scanning for improved lateral or axial resolution.
RESULTS
While some known probes can generate light upon x-ray scintillation, there has been an emergent recognition that excitation of molecular probes by x-ray-induced Cherenkov light is also possible. Emission of Cherenkov radiation requires a threshold energy of x-rays in the high kV or MV range, but has the advantage of being able to excite a broad range of optical molecular probes. In comparison, most scintillating agents are more readily activated by lower keV x-ray energies but are composed of crystalline inorganic constituents, although some organic biocompatible agents have been designed as well. Methods to create high-resolution structured x-ray-optical images are now available, based upon unique scanning approaches and/or a priori knowledge of the scanned x-ray beam geometry. Further improvements in spatial resolution can be achieved by careful system design and algorithm optimization. Current applications of these hybrid x-ray-optical approaches include imaging of tissue oxygenation and pH as well as of certain fluorescent proteins.
CONCLUSIONS
Discovery of x-ray-excited reporters combined with optimized x-ray scan sequences can improve imaging resolution and sensitivity.
Topics: Luminescence; Molecular Imaging; Optical Imaging; Phantoms, Imaging; Radiography; X-Rays
PubMed: 33386709
DOI: 10.1117/1.JBO.26.1.010902 -
Journal of Nuclear Medicine : Official... Oct 2020With the ability to noninvasively image and monitor molecular processes within tumors, molecular imaging represents a fundamental tool for cancer scientists. In the... (Review)
Review
With the ability to noninvasively image and monitor molecular processes within tumors, molecular imaging represents a fundamental tool for cancer scientists. In the current review, we describe emergent optical technologies for molecular imaging. We aim to provide the reader with an overview of the fundamental principles on which each imaging strategy is based, to introduce established and future applications, and to provide a rationale for selecting optical technologies for molecular imaging depending on disease location, biology, and anatomy. To accelerate clinical translation of imaging techniques, we also describe examples of practical applications in patients. Elevating these techniques into standard-of-care tools will transform patient stratification, disease monitoring, and response evaluation.
Topics: Humans; Luminescent Measurements; Microscopy, Fluorescence; Molecular Imaging; Neoplasms; Optical Imaging; Photoacoustic Techniques; Standard of Care
PubMed: 32764124
DOI: 10.2967/jnumed.119.238279 -
Journal of Biomedical Optics May 2023This third biennial intraoperative molecular imaging (IMI) conference shows how optical contrast agents have been applied to develop clinically significant endpoints... (Review)
Review
SIGNIFICANCE
This third biennial intraoperative molecular imaging (IMI) conference shows how optical contrast agents have been applied to develop clinically significant endpoints that improve precision cancer surgery.
AIM
National and international experts on IMI presented ongoing clinical trials in cancer surgery and preclinical work. Previously known dyes (with broader applications), new dyes, novel nonfluorescence-based imaging techniques, pediatric dyes, and normal tissue dyes were discussed.
APPROACH
Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center's third clinical trials update on IMI were selected to discuss their clinical trials and endpoints.
RESULTS
Dyes that are FDA-approved or currently under clinical investigation in phase 1, 2, and 3 trials were discussed. Sections on how to move benchwork research to the bedside were also included. There was also a dedicated section for pediatric dyes and nonfluorescence-based dyes that have been newly developed.
CONCLUSIONS
IMI is a valuable adjunct in precision cancer surgery and has broad applications in multiple subspecialties. It has been reliably used to alter the surgical course of patients and in clinical decision making. There remain gaps in the utilization of IMI in certain subspecialties and potential for developing newer and improved dyes and imaging techniques.
Topics: Humans; Child; Neoplasms; Contrast Media; Molecular Imaging; Coloring Agents
PubMed: 37193364
DOI: 10.1117/1.JBO.28.5.050901 -
International Journal of Molecular... Feb 2023Immunotherapy constitutes a paradigm shift in cancer treatment. Its FDA approval for several indications has yielded improved prognosis for cases where traditional... (Review)
Review
Immunotherapy constitutes a paradigm shift in cancer treatment. Its FDA approval for several indications has yielded improved prognosis for cases where traditional therapy has shown limited efficiency. However, many patients still fail to benefit from this treatment modality, and the exact mechanisms responsible for tumor response are unknown. Noninvasive treatment monitoring is crucial for longitudinal tumor characterization and the early detection of non-responders. While various medical imaging techniques can provide a morphological picture of the lesion and its surrounding tissue, a molecular-oriented imaging approach holds the key to unraveling biological effects that occur much earlier in the immunotherapy timeline. Magnetic resonance imaging (MRI) is a highly versatile imaging modality, where the image contrast can be tailored to emphasize a particular biophysical property of interest using advanced engineering of the imaging pipeline. In this review, recent advances in molecular-MRI based cancer immunotherapy monitoring are described. Next, the presentation of the underlying physics, computational, and biological features are complemented by a critical analysis of the results obtained in preclinical and clinical studies. Finally, emerging artificial intelligence (AI)-based strategies to further distill, quantify, and interpret the image-based molecular MRI information are discussed in terms of perspectives for the future.
Topics: Humans; Artificial Intelligence; Magnetic Resonance Imaging; Neoplasms; Immunotherapy; Molecular Imaging
PubMed: 36834563
DOI: 10.3390/ijms24043151 -
Trends in Biotechnology Feb 2020The spatial distribution of molecules and cells is fundamental to understanding biological systems. Traditionally, microscopies based on electromagnetic waves such as... (Review)
Review
The spatial distribution of molecules and cells is fundamental to understanding biological systems. Traditionally, microscopies based on electromagnetic waves such as visible light have been used to localize cellular components by direct visualization. However, these techniques suffer from limitations of transmissibility and throughput. Complementary to optical approaches, biochemical techniques such as crosslinking can colocalize molecules without suffering the same limitations. However, biochemical approaches are often unable to combine individual colocalizations into a map across entire cells or tissues. Microscopy-by-sequencing techniques aim to biochemically colocalize DNA-barcoded molecules and, by tracking their thus unique identities, reconcile all colocalizations into a global spatial map. Here, we review this new field and discuss its enormous potential to answer a broad spectrum of questions.
Topics: DNA Barcoding, Taxonomic; High-Throughput Nucleotide Sequencing; Microscopy; Molecular Imaging
PubMed: 31416630
DOI: 10.1016/j.tibtech.2019.06.001 -
Bioconjugate Chemistry Feb 2020Gold nanoparticles (AuNP) have been extensively developed as contrast agents, theranostic platforms, and probes for molecular imaging. This popularity has yielded a... (Review)
Review
Gold nanoparticles (AuNP) have been extensively developed as contrast agents, theranostic platforms, and probes for molecular imaging. This popularity has yielded a large number of AuNP designs that vary in size, shape, surface functionalization, and assembly, to match very closely the requirements for various imaging applications. Hence, AuNP based probes for molecular imaging allow the use of computed tomography (CT), fluorescence, and other forms of optical imaging, photoacoustic imaging (PAI), and magnetic resonance imaging (MRI), and other newer techniques. The unique physicochemical properties, biocompatibility, and highly developed chemistry of AuNP have facilitated breakthroughs in molecular imaging that allow the detection and imaging of physiological processes with high sensitivity and spatial resolution. In this Review, we summarize the recent advances in molecular imaging achieved using novel AuNP structures, cell tracking using AuNP, targeted AuNP for cancer imaging, and activatable AuNP probes. Finally, the perspectives and current limitations for the clinical translation of AuNP based probes are discussed.
Topics: Animals; Cell Tracking; Gold; Humans; Magnetic Resonance Imaging; Metal Nanoparticles; Molecular Imaging; Optical Imaging; Photoacoustic Techniques; Tomography, X-Ray Computed
PubMed: 31682405
DOI: 10.1021/acs.bioconjchem.9b00669