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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 -
Circulation. Cardiovascular Imaging Mar 2020
Topics: Atherosclerosis; Humans; Molecular Imaging; Positron-Emission Tomography
PubMed: 32164452
DOI: 10.1161/CIRCIMAGING.120.010494 -
Expert Review of Molecular Diagnostics Dec 2020: Only 20-40% of patients respond to therapy with immune checkpoint inhibitors (ICIs). Therefore, the early identification of subjects that can benefit from such... (Review)
Review
: Only 20-40% of patients respond to therapy with immune checkpoint inhibitors (ICIs). Therefore, the early identification of subjects that can benefit from such therapeutic regimen is mandatory. : The immunobiological mechanisms of ICIs are briefly illustrated. Furthermore, the limitations of traditional radiological approaches are covered. Then, the pros and cons of molecular imaging through positron emission computed tomography (PET/CT) are reviewed, with a particular focus on f-fluorodeoxyglucose (F-FDG) and PET-derived metabolic parameters. Lastly, translational perspective of radiopharmaceuticals others than F-FDG such as zirconium (Zr) or fluorine-18 (F) labeled monoclonal antibodies (e.g.Zr-atezolizumab, Zr-nivolumab) binding to specific biomarkers are discussed. : Molecular imaging presents a prominent role for the management of oncological patients treated with ICIs. Preliminary clinical data indicate that PET/CT with F-FDG is useful for assessing the response to treatment and for the imaging of immune-related adverse effects. Nevertheless, the methodological approach (iPERCIST, PERCIMT, or others) to be used for an optimal diagnostic accuracy and patients' evaluation is still a debated issue. PET/CT with radioligands directed toward ICIs biomarkers, although is still in a translational phase, holds the promise of accurately predicting the response to treatment and revealing the acquired resistance to immunotherapy.
Topics: Biomarkers, Tumor; Humans; Medical Oncology; Molecular Imaging; Multimodal Imaging; Neoplasms; Prognosis; Reproducibility of Results; Sensitivity and Specificity
PubMed: 33215963
DOI: 10.1080/14737159.2020.1854090 -
Nanoscale Apr 2020As the complications of atherosclerosis such as myocardial infarction and stroke are still one of the leading causes of mortality worldwide, the development of new... (Review)
Review
As the complications of atherosclerosis such as myocardial infarction and stroke are still one of the leading causes of mortality worldwide, the development of new diagnostic tools for the early detection of plaque instability and thrombosis is urgently needed. Advanced molecular imaging probes based on functional nanomaterials in combination with cutting edge imaging techniques are now paving the way for novel and unique approaches to monitor the inflammatory progress in atherosclerosis. This review focuses on the development of various molecular probes for the diagnosis of plaques and thrombosis in atherosclerosis, along with perspectives of their diagnostic applications in cardiovascular diseases. Specifically, we summarize the biological targets that can be used for atherosclerosis and thrombosis imaging. Then we describe the emerging molecular imaging techniques based on the utilization of engineered nanoprobes together with their challenges in clinical translation.
Topics: Animals; Atherosclerosis; Disease Progression; Humans; Molecular Imaging; Molecular Probes; Multimodal Imaging; Nanostructures; Plaque, Atherosclerotic; Thrombosis
PubMed: 32239038
DOI: 10.1039/d0nr00599a -
Contrast Media & Molecular Imaging 2022In recent years, imaging technology has made rapid progress to improve the sensitivity of tumor diagnostic. With the development of genetic engineering and synthetic... (Review)
Review
In recent years, imaging technology has made rapid progress to improve the sensitivity of tumor diagnostic. With the development of genetic engineering and synthetic biology, various genetically encoded molecular imaging probes have also been extensively developed. As a biomedical imaging method with excellent detectable sensitivity and spatial resolution, genetically encoded molecular imaging has great application potential in the visualization of cellular and molecular functions during tumor development. Compared to chemosynthetic dyes and nanoparticles with an imaging function, genetically encoded molecular imaging probes can more easily label specific cells or proteins of interest in tumor tissues and have higher stability and tissue contrast Therefore, genetically encoded molecular imaging probes have attracted increasing attention from researchers in engineering and biomedicine. In this review, we aimed to introduce the genetically encoded molecular imaging probes and further explained their applications in tumor imaging.
Topics: Humans; Molecular Imaging; Molecular Probes; Nanoparticles; Neoplasms
PubMed: 36101803
DOI: 10.1155/2022/5473244 -
Genesis (New York, N.Y. : 2000) Sep 2022Craniofacial and appendicular bone homeostasis is dynamically regulated by a balance between bone formation and resorption by osteoblasts and osteoclasts, respectively.... (Review)
Review
Craniofacial and appendicular bone homeostasis is dynamically regulated by a balance between bone formation and resorption by osteoblasts and osteoclasts, respectively. Despite the developments in multiple imaging techniques in bone biology, there are still technical challenges and limitations in the investigation of spatial/anatomical location of rare stem/progenitor cells and their molecular regulation in tooth and craniofacial bones of living animals. Recent advances in live animal imaging techniques for the craniofacial and dental apparatus can provide new insights in real time into bone stem/progenitor cell dynamics and function in vivo. Here, we review the current inventions and applications of the noninvasive intravital imaging technique and its practical uses and limitations in the analysis of stem/progenitor cells in craniofacial and dental apparatus in vivo. Furthermore, we also explore the potential applications of intravital microscopy in the dental field.
Topics: Animals; Bone and Bones; Intravital Microscopy; Molecular Imaging; Osteoclasts; Stem Cells
PubMed: 35980285
DOI: 10.1002/dvg.23498 -
Methods in Molecular Biology (Clifton,... 2022Molecular imaging (MI) is a non-invasive growing technology that allows the investigation of cellular and molecular processes in basic and clinical research and...
Molecular imaging (MI) is a non-invasive growing technology that allows the investigation of cellular and molecular processes in basic and clinical research and medicine. Luminescent proteins and radionuclides can be associated to target molecules providing high-definition and real-time image of whole body in few minutes or hours. Several MI studies have enabled the determination of molecular partners, in vivo tracking, and fate of compounds in different disorders. Considering that galectins are multifaceted proteins with great impact in many biological events, here we describe methods and strategies to generate labeled galectins for in vivo non-invasive imaging studies.
Topics: Galectins; Luminescent Proteins; Molecular Imaging
PubMed: 35320534
DOI: 10.1007/978-1-0716-2055-7_18 -
Accounts of Chemical Research Aug 2021This Account summarizes recent advances in the chemistry of fluorocarbon nanoemulsion (FC NE) functionalization. We describe new families of fluorous molecules, such as...
This Account summarizes recent advances in the chemistry of fluorocarbon nanoemulsion (FC NE) functionalization. We describe new families of fluorous molecules, such as chelators, fluorophores, and peptides, that are soluble in FC oils. These materials have helped transform the field of molecular imaging by enabling sensitive and cell-specific imaging using magnetic resonance imaging (MRI), positron emission tomography (PET), and fluorescence detection. FC emulsions, historically considered for artificial blood substitutes, are routinely used for ultrasound imaging in clinic and have a proven safety profile and a well-characterized biodistribution and pharmacokinetics. The inertness of fluorocarbons contributes to their low toxicity but makes functionalization difficult. The high electronegativity of fluorine imparts very low cohesive energy density and Lewis basicity to heavily fluorinated compounds, making dissolution of metal ions and organic molecules challenging. Functionalization is further complicated by colloidal instability toward heat and pH, as well as limited availability of biocompatible surfactants.We have devised new fluorous chelators that overcome solubility barriers and are able to bind a range of metal ions with high thermodynamic stability and biocompatibility. NE harboring chelators in the fluorous phase are a powerful platform for the development of multimodal imaging agents. These compositions rapidly capture metal ions added to the aqueous phase, thereby functionalizing NEs in useful ways. For example, Fe encapsulation imparts a strong paramagnetic relaxation effect on F that dramatically accelerates F MRI data acquisition times and hence sensitivity in cell tracking applications. Alternatively, Zr encapsulation creates a sensitive and versatile PET probe for inflammatory macrophage detection. Adding lanthanides, such as Eu, renders NE luminescent. Beyond chelators, this Account further covers our progress in formulating NEs with fluorophores, such as cyanine or BODIPY dyes, with their utility demonstrated in fluorescence imaging, biosensing, flow cytometry and histology. Fluorous dyes soluble in FC oils are also key enablers for nascent whole-body imaging technologies such as cryo-fluorescence tomography (CFT). Additionally, fluorous cell-penetrating peptides inserted on the NE surface increase the uptake of NE by ∼8-fold in weakly phagocytic stem cells and lymphocytes used in immunotherapy, resulting in significant leaps in detection sensitivity
Topics: Fluorine; Magnetic Resonance Imaging; Molecular Imaging; Positron-Emission Tomography
PubMed: 34259521
DOI: 10.1021/acs.accounts.1c00278 -
Radiology Aug 2022Immunotherapy has transformed the treatment landscape of many cancers, with durable responses in disease previously associated with a poor prognosis. Patient selection... (Review)
Review
Immunotherapy has transformed the treatment landscape of many cancers, with durable responses in disease previously associated with a poor prognosis. Patient selection remains a challenge, with predictive biomarkers an urgent unmet clinical need. Current predictive biomarkers, including programmed death-ligand 1 (PD-L1) (measured with immunohistochemistry), are imperfect. Promising biomarkers, including tumor mutation burden and tumor infiltrating lymphocyte density, fail to consistently predict response and have yet to translate to routine clinical practice. Heterogeneity of immune response within and between lesions presents a further challenge where fluorine 18 fluorodeoxyglucose PET/CT has a potential role in assessing response, stratifying treatment, and detecting and monitoring immune-related toxicities. Novel radiopharmaceuticals also present a unique opportunity to define the immune tumor microenvironment to better predict which patients may respond to therapy, for example by means of in vivo whole-body PD-L1 and CD8+ T cell expression imaging. In addition, longitudinal molecular imaging may help further define dynamic changes, particularly in cases of immunotherapy resistance, helping to direct a more personalized therapeutic approach. This review highlights current and emerging applications of molecular imaging to stratify, predict, and monitor molecular dynamics and treatment response in areas of clinical need.
Topics: B7-H1 Antigen; Biomarkers, Tumor; Fluorodeoxyglucose F18; Humans; Immunotherapy; Molecular Imaging; Neoplasms; Positron Emission Tomography Computed Tomography; Tumor Microenvironment
PubMed: 35762888
DOI: 10.1148/radiol.212481 -
Journal of Echocardiography Jun 2020Similar to what has already occurred in cancer medicine, the management of cardiovascular conditions will likely be improved by non-invasive molecular imaging... (Review)
Review
Similar to what has already occurred in cancer medicine, the management of cardiovascular conditions will likely be improved by non-invasive molecular imaging technologies that can provide earlier or more accurate diagnosis. These techniques are already having a positive impact in pre-clinical research by providing insight into pathophysiology or efficacy of new therapies. Contrast enhanced ultrasound (CEU) molecular imaging is a technique that relies on the ultrasound detection of targeted microbubble contrast agents to examine molecular or cellular events that occur at the blood pool-endothelial interface. CEU molecular imaging techniques have been developed that are able to provide unique information on atherosclerosis, ischemia reperfusion injury, angiogenesis, vascular inflammation, and thrombus formation. Accordingly, CEU has the potential to be used in a wide variety of circumstances to detect disease early or at the bedside, and to guide appropriate therapy based on vascular phenotype. This review will describe the physical basis for CEU molecular imaging, and the specific disease processes for the pre-clinical translational research experience.
Topics: Cardiovascular Diseases; Contrast Media; Humans; Microbubbles; Molecular Imaging; Ultrasonography
PubMed: 32056137
DOI: 10.1007/s12574-020-00463-z