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Theranostics: A New Holistic Approach in Nanomedicine
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Ankit Rochani, Sreejith Raveendran
Ultrasound technology, with an increase in frequency, also helps generate localized heating potential. For instance, 3 MHz ultrasound may provide heating at 0.5 cm deeper in the tissue. The temperature of 40 °C was generated within 4 min of ultrasound exposure in n = 18 healthy volunteers [41]. This suggests that the technique could be used to generate a theranostic controlled delivery platform. Typically, microbubbles are used as ultrasound-based theranostic agents. These microbubbles are synthesized using proteins, polysaccharides, polymers, lipids, and surfactants. As the name suggests, microbubbles consist of biomaterial shells filled with an inner core containing air, nitrogen, sulfur hexafluoride (SF6), and perfluorocarbons (PFCs) [42]. Microbubbles expand and relax when exposed to ultrasound frequencies. These vibrations increase at a higher frequency. This makes these systems better for imaging abnormalities rather than the normal tissues. The vibrations are the harmonic signals, which ultrasound can listen to and create enhanced greyscale images [43]. The first commercialized air-filed microbubble preparation, called albunex, was used for diagnostic applications. Today, we have both conventional microbubbles (beyond the scope of discussion) and nanobubble systems that are being explored for theranostic applications [42].
Ultrasound Physics
Published in Debbie Peet, Emma Chung, Practical Medical Physics, 2021
Ultrasound contrast agents: Vascular ultrasound contrast agents take the form of tiny “microbubbles” that are introduced to the blood stream to enhance the ultrasound signal from blood flow. Microbubbles can be generated through agitation of saline and are commercially available as vials of encapsulated microbubbles. Each vial contains millions of 1–10 µm diameter bubbles containing a biocompatible inert gas, encapsulated in a lipid shell. These improve the visibility of vessels and can potentially be targeted to adhere to thrombus or tumours. Contrast-enhanced ultrasound (CEUS) imaging is often used as an adjunct to conventional B-mode imaging to distinguish between benign and malignant tumours through identifying hypervascularity associated with tumour growth.
Renal cancer
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Conrad von Stempel, Lee Alexander Grant, Miles Walkden, Navin Ramachandran
Contrast-enhanced ultrasound (CEUS) allows dynamic assessment of a lesion with real-time observation of enhancement characteristics when microbubble contrast agents are used. The microbubbles used are safe in patients with renal impairment. CEUS is more sensitive than CECT in detecting vascularity within a lesion (89). CEUS therefore has a role in detecting enhancement in some subtypes of RCC that tend to be hypovascular and characterize complex cystic masses where CECT is inconclusive (90). CEUS has a high sensitivity for diagnosing malignant renal masses reported between 88% and 99%, with a specificity between 50% and 80% (80,91–95). CEUS also has good reported interobserver agreement when assessing video loops of enhancement in renal lesions (Figure 13.6) (96).
Scale-up production, characterization and toxicity of a freeze-dried lipid-stabilized microbubble formulation for ultrasound imaging and therapy
Published in Journal of Liposome Research, 2020
Johan Unga, Saori Kageyama, Ryo Suzuki, Daiki Omata, Kazuo Maruyama
Microbubbles have a long history of being used for ultrasound (US) applications. Initially, they were used for US imaging and are considered safe and generally have virtually no side-effects from either the bubbles or the US energy applied for imaging, at least for single or limited use (Gramiak and Shah 1968, Landmark et al.2008). Recently, there has been a great interest in using bubbles and US also for therapeutic applications. Bubbles can be made to oscillate in size or collapse leading to jet streams (Kudo et al.2009, Collis et al.2010, Bouakaz et al.2016). Both processes can open up barriers in the body, such as cell membranes and endothelia, and this can lead to improved delivery of drugs or other molecules or particles across those barriers. This has been utilized for various applications as small drug delivery (Abdalkader et al.2015), delivery of macromolecules (Negishi et al.2008, Unga and Hashida 2014) and drug carriers such as liposomes (Klibanov et al.2010, Lentacker et al.2010). In both imaging and therapeutic applications bubbles are injected locally or i.v. and this is combined with an external US source.
Sonopermeation to improve drug delivery to tumors: from fundamental understanding to clinical translation
Published in Expert Opinion on Drug Delivery, 2018
Sofie Snipstad, Einar Sulheim, Catharina de Lange Davies, Chrit Moonen, Gert Storm, Fabian Kiessling, Ruth Schmid, Twan Lammers
Sonopermeation is a technology that is rapidly moving towards clinical practice, based on promising results obtained in proof-of-principle studies in animal models. Multiple clinical trials are currently ongoing, of which the vast majority are exploiting combinations of clinically approved microbubbles and drugs. While it is sensible to break new ground with established methods combining already approved components, the development is now going in the direction of more specialized systems, produced especially for drug delivery. It has been demonstrated pre-clinically that microbubbles developed for therapy can be superior to the clinically approved alternatives, tailored for imaging applications. In addition, many pre-clinical experiments involve ultrasound settings outside the range of diagnostic ultrasound scanners, indicating a need for developing transducers specialized for therapeutic applications. On the other side, there are obviously very appealing advantages associated with the use of systems that are already approved as the road to clinical use is much shorter both financially and regulatory.
Effects of a microbubble ultrasound contrast agent on high-intensity focused ultrasound for uterine fibroids: a randomised controlled trial
Published in International Journal of Hyperthermia, 2018
Yan Chen, Jing Jiang, Yuhua Zeng, Xiaobing Tian, Miao Zhang, Hong Wu, Honggui Zhou
Currently, contrast-enhanced ultrasound has been widely used to evaluate the treatment results of HIFU in China. Several studies have also shown that contrast-enhanced ultrasound agents could enhance the ablation effect because the microbubbles change the acoustic characteristics of tissues, improve the thermal and cavitation effects, and thus the energy deposition in the target area is easier and the therapeutic effect increases [7,8]. However, if the microbubble concentration is too high, it will damage the outside tissue. On the other hand, if the microbubble concentration is too low, the microbubble-enhancing effect will not be obvious. Therefore, it is necessary to choose the appropriate dose of microbubble to enhance the treatment effects of HIFU safely and effectiveness. Peng et al. [9] retrospectively analysed 291 patients and showed that SonoVue enhanced the effect of HIFU ablation of uterine fibroids when HIFU treatment started 10 min after SonoVue injection (2 ml). SonoVue has a short half-life. Following intravenous administration, the blood level curve showed an elimination half-life of 6 min. More than 80% of the administered SonoVue was removed after 11 min [10]. In this study, we conducted a randomised controlled trial to investigate the enhancement effects of ultrasound contrast agent SonoVue on HIFU, to see if higher the concentration of contrast agent has a more obvious enhancement effect, and to provide a clinical value for further study on the optimal concentration of contrast agent and the safest time for starting sonication.