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Biomedical Imaging Molecular Imaging
Published in Lawrence S. Chan, William C. Tang, Engineering-Medicine, 2019
Christian J. Konopka, Emily L. Konopka, Lawrence W. Dobrucki
There are two general categories of contrast agents, targeted or non-targeted. Most CT and MRI contrast agents are non-targeted as either blood pool, gastrointestinal, hepatobiliary, or extracellular agents. These agents typically use passive qualities by either being injected directly to the needed site of contrast (blood pool agents) or by relying on their natural secretory routes to bring them to the organs of interest (hepatobiliary and gastrointestinal agents). These are considered non-targeted or passively targeted agents because they do not require affinity for a specific receptor or molecule to direct their accumulation in the tissue of interest.
Uro-Angiographic Contrast Agents—The Holy Grail
Published in Christoph de Haën, X-Ray Contrast Agent Technology, 2019
One way of avoiding prolonged persistence in the body while maintaining blood pool agent behavior was accorded by the preparation of various solid colloidal iodinated organic products that in the body could be biodegraded to established water-soluble contrast agents (e.g., Fischer 1977a,b; Lauteala, Kormano, and Violante 1984). Unluckily, from an excretion and safety standpoint, their intravascular use never looked promising, not to speak of their excessive potential cost of manufacturing. The same can be said about metal cluster compounds, envisioned more recently (Yu and Watson 1999; Berger et al. 2011). Since the disappearance of THOROTRAST no company has taken the risks associated with the development of X-ray contrast agents based on colloidal solid particles.
Microcomputed Tomography
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
To improve the contrast for imaging soft tissue and vasculature, iodinated contrast agents can be introduced to alter the x-ray attenuation characteristics of the target organ or tissue. Although there are clinically available iodinated contrast agents, they are not often used due to the relatively long scan times required for imaging compared with the metabolic rate of the rodent. To ensure constant enhancement through the imaging session, the clinical agents must be introduced via a power injection with a constant infusion rate. Alternatively, blood pool agents have been developed for preclinical applications. These blood pool agents, injected via the tail vein, recirculate in the vasculature for hours to provide exquisite contrast between the blood and surrounding tissue.
Targeting of microbubbles: contrast agents for ultrasound molecular imaging
Published in Journal of Drug Targeting, 2018
Shiying Wang, John A. Hossack, Alexander L. Klibanov
The most stable gas-filled microbubbles with outstanding robustness and storage are made using a solid thick material (e.g. glass shell) [15]. They may vary from several to several dozen micrometers in size, and the shell may have micrometer thickness. These bubbles are stable in the aqueous media for years (bubbles of this kind in an aqueous dispersion float to the top of the media and remain unchanged there for several years). However, medical imaging use of these particles is highly unlikely, because they are not biodegradable and will not exit the body. Biocompatible biodegradable polymers are available to replace glass, for instance, polylactide/poly-lactide-co-glycolide (used in degradable surgical sutures). Polymer bubbles can be made by emulsion processes and include lyophilisation or spray drying as the final step, to remove the internal core and create an internal void to be filled with gas. This formulation is very appropriate for the long-term storage stability: without lyophilisation, in the aqueous medium, these polymers will hydrolyse and degrade. PLGA-based particles had been in preclinical development and clinical trials; for one of such blood pool agents, AI-700/Imagify, from Acusphere (Boston, MA) Phase 3 clinical trials were completed [16] but it had not been approved by regulatory authorities in US and application had been withdrawn in Europe. Another agent, made of a different polymer, cyanoacrylate, the base of a biocompatible surgical glue, Sonovist/SHU563A (Schering, Berlin), also quite stable on storage, had very reasonable circulation half-life in the bloodstream, but also did not make a transition to clinical use. Alternative versions of this polymer bubble are now under intense assessment in preclinical setting [17]. Recently, a hybrid approach has been proposed, a combination of silica and polymer in a particle formulation [18], but it is too early to tell whether it will progress towards clinical use.