First Multimodal Embolization Particles Visible on X-ray/Computed Tomography and Magnetic Resonance Imaging

Bartling, Sönke; Budjan, Johannes; Aviv, Hagit; Haneder, Stefan; Kraenzlin, Bettina; Michaely, Henrik J.; Margel, Shlomo; Diehl, Steffen J.; Semmler, Willi; Gretz, Norbert; Schönberg, Stefan O.; Sadick, Maliha

doi:10.1097/rli.0b013e318205af53

Cited by 37 publications

(36 citation statements)

References 38 publications

(48 reference statements)

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“…Over the last several years, nano- and microparticles for embolization therapies have been developed that can be imaged by CT and MRI. Examples of such particles include chitosan microspheres loaded with SPIO that were detectable by MRI (111) and multimodal particles of 40-200 μm size that consist of a copolymerized methacryloyloxyethyl triiodobenzaote (MAOETIB) core coated with ~150 nm large USPIO which are thus detectable by x-ray and MR imaging (112). Transarterial chemoembolization (TACE) is another procedure that may benefit from the use of novel theranostic nano-/microparticle agents, which have been excellently reviewed in (113).…”

Section: Nanoparticle-based Theranosticsmentioning

confidence: 99%

Nanoparticles for Imaging: Top or Flop?

Kießling¹,

Mertens²,

Grimm³

et al. 2014

Radiology

192

146

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Nanoparticles are frequently suggested as diagnostic agents. However, except for iron oxide nanoparticles, diagnostic nanoparticles have been barely incorporated into clinical use so far. This is predominantly due to difficulties in achieving acceptable pharmacokinetic properties and reproducible particle uniformity as well as to concerns about toxicity, biodegradation, and elimination. Reasonable indications for the clinical utilization of nanoparticles should consider their biologic behavior. For example, many nanoparticles are taken up by macrophages and accumulate in macrophage-rich tissues. Thus, they can be used to provide contrast in liver, spleen, lymph nodes, and inflammatory lesions (eg, atherosclerotic plaques). Furthermore, cells can be efficiently labeled with nanoparticles, enabling the localization of implanted (stem) cells and tissue-engineered grafts as well as in vivo migration studies of cells. The potential of using nanoparticles for molecular imaging is compromised because their pharmacokinetic properties are difficult to control. Ideal targets for nanoparticles are localized on the endothelial luminal surface, whereas targeted nanoparticle delivery to extravascular structures is often limited and difficult to separate from an underlying enhanced permeability and retention (EPR) effect. The majority of clinically used nanoparticle-based drug delivery systems are based on the EPR effect, and, for their more personalized use, imaging markers can be incorporated to monitor biodistribution, target site accumulation, drug release, and treatment efficacy. In conclusion, although nanoparticles are not always the right choice for molecular imaging (because smaller or larger molecules might provide more specific information), there are other diagnostic and theranostic applications for which nanoparticles hold substantial clinical potential.

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Section: Nanoparticle-based Theranosticsmentioning

confidence: 99%

Nanoparticles for Imaging: Top or Flop?

Kießling¹,

Mertens²,

Grimm³

et al. 2014

Radiology

192

146

View full text Add to dashboard Cite

show abstract

“…The embolization is continued until a desired embolization endpoint is reached or reflux of contrast material into non-target vessels is observed, without specific feedback on DEB or drug location. In order to address this lack of feedback, investigators have developed image-able spherical beads or other particles that can be visualized with magnetic resonance [78–83] and X-ray-based (e.g., fluoroscopy and CT) imaging [84, 85] or both [86]. Image-ability is obtained by trapping the relevant contrast material within the porous particle/bead structure or chemically attaching contrast to the polymer backbone.…”

Section: Future Directions In Deb-tacementioning

confidence: 99%

Locoregional drug delivery using image-guided intra-arterial drug eluting bead therapy

Lewis

Dreher

2012

Journal of Controlled Release

102

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Lipiodol-based transarterial chemoembolization (TACE) has been performed for over 3 decades for the treatment of solid tumors and describes the infusion of chemotherapeutic agents followed by embolization with particles. TACE is an effective treatment for inoperable hepatic tumors, especially hypervascular tumors such as hepatocellular carcinoma. Recently, drug eluting beads (DEBs), in which a uniform embolic material is loaded with a drug and delivered in a single image-guided step, have been developed to reduce the variability in a TACE procedure. DEB-TACE results in localization of drug to targeted tumors while minimizing systemic exposure to chemotherapeutics. Once localized in the tissue, drug is eluted from the DEB in a controlled manner and penetrates hundreds of microns of tissue from the DEB surface. Necrosis is evident surrounding a DEB in tissue days to months after therapy; however, the contribution of drug and ischemia is currently unknown. Future advances in DEB technology may include image-ability, DEB size tailored to tumor anatomy and drug combinations.

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“…In contrast to “conventional” TACE, DEB-TACE lacks the intraprocedural imaging feedback of lipiodol deposition in the target tumor which is seen with fluoroscopy or CT. In order to address this lack of feedback, investigators have developed image-able beads that can be visualized with magnetic resonance (17–20) and fluoroscopic imaging (21–22) or both (23). Knowledge of bead distribution during a procedure may provide useful real-time feedback to modify the intervention and tailor the procedure to a specific patient.…”

Section: Introductionmentioning

confidence: 99%

Radiopaque Drug-Eluting Beads for Transcatheter Embolotherapy: Experimental Study of Drug Penetration and Coverage in Swine

Dreher

Sharma

Woods

et al. 2012

Journal of Vascular and Interventional Radiology

115

100

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Purpose The objective of this study was to determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEB) in normal swine liver and kidney following transcatheter arterial chemoembolization (TACE). The influence of bead size (70–150µm or 100–300µm) was compared with regard to tissue penetration and spatial distribution of the bead as well as eventual drug coverage (i.e., amount of tissue exposed to drug). Materials and Methods Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three dimensional tissue penetration of image-able DEB was investigated ex vivo with microCT. Drug penetration from the bead surface and drug coverage was evaluated with epi-fluorescence microscopy while cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with H&E. Results MicroCT demonstrated that 70–150µm DEB were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (~300µm) for both DEBs with a maximum tissue drug concentration at 1hr coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70–150µm DEBs resulted in ~2-fold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hr but increased at 24 and 168 hrs. Conclusions Smaller DEBs penetrated further into targeted tissue (macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (microscopic) in swine.

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First Multimodal Embolization Particles Visible on X-ray/Computed Tomography and Magnetic Resonance Imaging

Cited by 37 publications

References 38 publications

Nanoparticles for Imaging: Top or Flop?

Nanoparticles for Imaging: Top or Flop?

Locoregional drug delivery using image-guided intra-arterial drug eluting bead therapy

Radiopaque Drug-Eluting Beads for Transcatheter Embolotherapy: Experimental Study of Drug Penetration and Coverage in Swine

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