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Chemical Science Nov 2023Ultrasound (US) is routinely used for diagnostic imaging and increasingly employed for therapeutic applications. Materials that act as cavitation nuclei can improve the... (Review)
Review
Ultrasound (US) is routinely used for diagnostic imaging and increasingly employed for therapeutic applications. Materials that act as cavitation nuclei can improve the resolution of US imaging, and facilitate therapeutic US procedures by promoting local drug delivery or allowing temporary biological barrier opening at moderate acoustic powers. Polymeric materials offer a high degree of control over physicochemical features concerning responsiveness to US, tuning chain composition, length and rigidity. This level of control cannot be achieved by materials made of lipids or proteins. In this perspective, we present key engineered polymeric materials that respond to US, including microbubbles, gas-stabilizing nanocups, microcapsules and gas-releasing nanoparticles, and discuss their formulation aspects as well as their principles of US responsiveness. Focusing on microbubbles as the most common US-responsive polymeric materials, we further evaluate the available chemical toolbox to engineer polymer shell properties and enhance their performance in US imaging and US-mediated drug delivery. Additionally, we summarize emerging applications of polymeric microbubbles in molecular imaging, sonopermeation, and gas and drug delivery, based on refinement of MB shell properties. Altogether, this manuscript provides new perspectives on US-responsive polymeric designs, envisaging their current and future applications in US imaging and therapy.
PubMed: 37969594
DOI: 10.1039/d3sc04339h -
Radiology. Cardiothoracic Imaging Aug 2023Paragangliomas are rare neuroendocrine tumors of extra-adrenal autonomic paraganglia origin. Paragangliomas rarely involve the heart, and they account for less than 1%...
Paragangliomas are rare neuroendocrine tumors of extra-adrenal autonomic paraganglia origin. Paragangliomas rarely involve the heart, and they account for less than 1% of primary cardiac tumors. Most cardiac paragangliomas are incidentally detected at echocardiography or CT or during the workup of symptomatic patients with high catecholamine levels. Paragangliomas are typically located around the great vessels, coronary arteries (atrioventricular groove), or the atria, which can be explained by the tumor origin from the paraganglia and the distribution of the cardiac plexus. At MRI, cardiac paragangliomas typically have low to intermediate signal on T1-weighted images and high signal on T2-weighted images. The tumors are strongly vascularized, with high uptake on first-pass perfusion images and a heterogeneous pattern on late gadolinium enhancement images. Functional imaging is indicated for diagnostic confirmation and to screen for additional tumor locations or metastatic disease. Surgical excision is the only curative treatment. Cardiac CT angiography or invasive angiography should be performed preoperatively to precisely delineate tumor vascularization. In particular, its relation with the coronary arteries should be determined, as paragangliomas can be perfused by the coronary arteries, posing additional surgical challenges and the need for coronary revascularization. This imaging essay reviews the characteristics of paragangliomas and the use of multimodality imaging for diagnosis and treatment. CT Angiography, Molecular Imaging, MR Imaging, PET/CT, Cardiac, Heart, Neoplasms-Primary © RSNA, 2023.
PubMed: 37693206
DOI: 10.1148/ryct.230049 -
Advanced Science (Weinheim,... Aug 2023Photoacoustic microscopy can image many biological molecules and nano-agents in vivo via low-scattering ultrasonic sensing. Insufficient sensitivity is a long-standing...
Photoacoustic microscopy can image many biological molecules and nano-agents in vivo via low-scattering ultrasonic sensing. Insufficient sensitivity is a long-standing obstacle for imaging low-absorbing chromophores with less photobleaching or toxicity, reduced perturbation to delicate organs, and more choices of low-power lasers. Here, the photoacoustic probe design is collaboratively optimized and a spectral-spatial filter is implemented. A multi-spectral super-low-dose photoacoustic microscopy (SLD-PAM) is presented that improves the sensitivity by ≈33 times. SLD-PAM can visualize microvessels and quantify oxygen saturation in vivo with ≈1% of the maximum permissible exposure, dramatically reducing potential phototoxicity or perturbation to normal tissue function, especially in imaging of delicate tissues, such as the eye and the brain. Capitalizing on the high sensitivity, direct imaging of deoxyhemoglobin concentration is achieved without spectral unmixing, avoiding wavelength-dependent errors and computational noises. With reduced laser power, SLD-PAM can reduce photobleaching by ≈85%. It is also demonstrated that SLD-PAM achieves similar molecular imaging quality using 80% fewer contrast agents. Therefore, SLD-PAM enables the use of a broader range of low-absorbing nano-agents, small molecules, and genetically encoded biomarkers, as well as more types of low-power light sources in wide spectra. It is believed that SLD-PAM offers a powerful tool for anatomical, functional, and molecular imaging.
Topics: Microscopy; Lasers; Ultrasonics; Light
PubMed: 37310419
DOI: 10.1002/advs.202302486 -
Journal of Personalized Medicine Mar 2024Molecular imaging is a key tool in the diagnosis and treatment of prostate cancer (PCa). Magnetic Resonance (MR) plays a major role in this respect with nuclear medicine... (Review)
Review
Molecular imaging is a key tool in the diagnosis and treatment of prostate cancer (PCa). Magnetic Resonance (MR) plays a major role in this respect with nuclear medicine imaging, particularly, Prostate-Specific Membrane Antigen-based, (PSMA-based) positron emission tomography with computed tomography (PET/CT) also playing a major role of rapidly increasing importance. Another key technology finding growing application across medicine and specifically in molecular imaging is the use of machine learning (ML) and artificial intelligence (AI). Several authoritative reviews are available of the role of MR-based molecular imaging with a sparsity of reviews of the role of PET/CT. This review will focus on the use of AI for molecular imaging for PCa. It will aim to achieve two goals: firstly, to give the reader an introduction to the AI technologies available, and secondly, to provide an overview of AI applied to PET/CT in PCa. The clinical applications include diagnosis, staging, target volume definition for treatment planning, outcome prediction and outcome monitoring. ML and AL techniques discussed include radiomics, convolutional neural networks (CNN), generative adversarial networks (GAN) and training methods: supervised, unsupervised and semi-supervised learning.
PubMed: 38541029
DOI: 10.3390/jpm14030287 -
EJNMMI Physics Jul 2023
PubMed: 37428285
DOI: 10.1186/s40658-023-00550-x -
Current Issues in Molecular Biology Mar 2024Iron is essential for many physiological processes, and the dysregulation of its metabolism is implicated in the pathogenesis of various diseases. Recent advances in... (Review)
Review
Iron is essential for many physiological processes, and the dysregulation of its metabolism is implicated in the pathogenesis of various diseases. Recent advances in iron metabolism research have revealed multiple complex pathways critical for maintaining iron homeostasis. Molecular imaging, an interdisciplinary imaging technique, has shown considerable promise in advancing research on iron metabolism. Here, we comprehensively review the multifaceted roles of iron at the cellular and systemic levels (along with the complex regulatory mechanisms of iron metabolism), elucidate appropriate imaging methods, and summarize their utility and fundamental principles in diagnosing and treating diseases related to iron metabolism. Utilizing molecular imaging technology to deeply understand the complexities of iron metabolism and its critical role in physiological and pathological processes offers new possibilities for early disease diagnosis, treatment monitoring, and the development of novel therapies. Despite technological limitations and the need to ensure the biological relevance and clinical applicability of imaging results, molecular imaging technology's potential to reveal the iron metabolic process is unparalleled, providing new insights into the link between iron metabolism abnormalities and various diseases.
PubMed: 38666905
DOI: 10.3390/cimb46040175 -
Journal of Nuclear Medicine : Official... Jul 2023Primary liver cancer is the third leading cause of cancer-related deaths, and its incidence and mortality are increasing worldwide. Hepatocellular carcinoma (HCC)...
Primary liver cancer is the third leading cause of cancer-related deaths, and its incidence and mortality are increasing worldwide. Hepatocellular carcinoma (HCC) accounts for 80% of primary liver cancer cases. Glypican-3 (GPC3) is a heparan sulfate proteoglycan that histopathologically defines HCC and represents an attractive tumor-selective marker for radiopharmaceutical imaging and therapy for this disease. Single-domain antibodies are a promising scaffold for imaging because of their favorable pharmacokinetic properties, good tumor penetration, and renal clearance. Although conventional lysine-directed bioconjugation can be used to yield conjugates for radiolabeling full-length antibodies, this stochastic approach risks negatively affecting target binding of the smaller single-domain antibodies. To address this challenge, site-specific approaches have been explored. Here, we used conventional and sortase-based site-specific conjugation methods to engineer GPC3-specific human single-domain antibody (HN3) PET probes. Bifunctional deferoxamine (DFO) isothiocyanate was used to synthesize native HN3 (nHN3)-DFO. Site-specifically modified HN3 (ssHN3)-DFO was engineered using sortase-mediated conjugation of triglycine-DFO chelator and HN3 containing an LPETG C-terminal tag. Both conjugates were radiolabeled with Zr, and their binding affinity in vitro and target engagement of GPC3-positive (GPC3) tumors in vivo were determined. Both Zr-ssHN3 and Zr-nHN3 displayed nanomolar affinity for GPC3 in vitro. Biodistribution and PET/CT image analysis in mice bearing isogenic A431 and A431-GPC3 xenografts, as well as in HepG2 liver cancer xenografts, showed that both conjugates specifically identify GPC3 tumors. Zr-ssHN3 exhibited more favorable biodistribution and pharmacokinetic properties, including higher tumor uptake and lower liver accumulation. Comparative PET/CT studies on mice imaged with both F-FDG and Zr-ssHN3 showed more consistent tumor accumulation for the single-domain antibody conjugate, further establishing its potential for PET imaging. Zr-ssHN3 showed clear advantages in tumor uptake and tumor-to-liver signal ratio over the conventionally modified Zr-nHN3 in xenograft models. Our results establish the potential of HN3-based single-domain antibody probes for GPC3-directed PET imaging of liver cancers.
Topics: Humans; Animals; Mice; Liver Neoplasms; Carcinoma, Hepatocellular; Single-Domain Antibodies; Radioisotopes; Glypicans; Positron Emission Tomography Computed Tomography; Antibodies, Monoclonal; Tissue Distribution; Cell Line, Tumor; Positron-Emission Tomography; Zirconium
PubMed: 36997331
DOI: 10.2967/jnumed.122.265171 -
Clinical and Experimental Medicine Jan 2024Humanity is suffering from cancer which has become a root cause of untimely deaths of individuals around the globe in the recent past. Nanotheranostics integrates... (Review)
Review
Humanity is suffering from cancer which has become a root cause of untimely deaths of individuals around the globe in the recent past. Nanotheranostics integrates therapeutics and diagnostics to monitor treatment response and enhance drug efficacy and safety. We hereby propose to discuss all recent cancer imaging and diagnostic tools, the mechanism of targeting tumor cells, and current nanotheranostic platforms available for cancer. This review discusses various nanotheranostic agents and novel molecular imaging tools like MRI, CT, PET, SPEC, and PAT used for cancer diagnostics. Emphasis is given to gold nanoparticles, silica, liposomes, dendrimers, and metal-based agents. We also highlight the mechanism of targeting the tumor cells, and the limitations of different nanotheranostic agents in the field of research for cancer treatment. Due to the complexity in this area, multifunctional and hybrid nanoparticles functionalized with targeted moieties or anti-cancer drugs show the best feature for theranostics that enables them to work on carrying and delivering active materials to the desired area of the requirement for early detection and diagnosis. Non-invasive imaging techniques have a specificity of receptor binding and internalization processes of the nanosystems within the cancer cells. Nanotheranostics may provide the appropriate medicine at the appropriate dose to the appropriate patient at the appropriate time.
Topics: Humans; Drug Delivery Systems; Theranostic Nanomedicine; Gold; Metal Nanoparticles; Neoplasms
PubMed: 38240834
DOI: 10.1007/s10238-023-01262-3 -
ACS Nano Oct 2023Optical imaging has become an indispensable technology in the clinic. The molecular design of cell-targeted and highly sensitive materials, the validation of specific... (Review)
Review
Optical imaging has become an indispensable technology in the clinic. The molecular design of cell-targeted and highly sensitive materials, the validation of specific disease biomarkers, and the rapid growth of clinically compatible instrumentation have altogether revolutionized the way we use optical imaging in clinical settings. One prime example is the application of cancer-targeted molecular imaging agents in both trials and routine clinical use to define the margins of tumors and to detect lesions that are "invisible" to the surgeons, leading to improved resection of malignant tissues without compromising viable structures. In this Perspective, we summarize some of the key research advances in chemistry, biology, and engineering that have accelerated the translation of optical imaging technologies for use in human patients. Finally, our paper comments on several research areas where further work will likely render the next generation of technologies for translational optical imaging.
Topics: Humans; Fluorescent Dyes; Neoplasms; Optical Imaging
PubMed: 37787658
DOI: 10.1021/acsnano.3c03564