Tumour hyperthermia and ablation in rats using a clinical MR‐HIFU system equipped with a dedicated small animal set‐up

Hijnen, Nicole M; Heijman, Edwin; Köhler, Max O.; Ylihautala, Mika; Ehnholm, Gösta; Simonetti, Arjan W.; Grüll, Holger

doi:10.3109/02656736.2011.648137

Cited by 70 publications

(55 citation statements)

References 48 publications

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“…To allow analysis of cell viability, a nicotinamide adenine dinucleotide (NADH) diaphorase staining was performed on the tumor sections according to a previously published protocol. [ 46 ] In addition, formaldehyde-fi xed (4% formaldehyde, 10 min) cryo-sections were stained with haematoxylin and eosin (H&E).…”

Section: Zirconium-89 Labeling Of Micelles : Labeling Of the Micellesmentioning

confidence: 99%

⁸⁹Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T₁‐Weighted MR Imaging

Starmans

Hummelink

Rossin

et al. 2015

Adv Healthcare Materials

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In this study, a new Zr- and Fe -labeled micelle nanoplatform ( Zr/Fe-DFO-micelles) for dual modality position emission tomography/magnetic resonance (PET/MR) imaging is investigated. The nanoplatform consists of self-assembling amphiphilic diblock copolymers that are functionalized with Zr-deferoxamine ( Zr-DFO) and Fe -deferoxamine (Fe-DFO) for PET and MR purposes, respectively. Zr displays favorable PET imaging characteristics with a 3.3 d half-life suitable for imaging long circulating nanoparticles. The nanoparticles are modified with Fe-DFO as MR T -contrast label instead of commonly used Gd -based chelates. As these micelles are cleared by liver and spleen, any long term Gd- related toxicity such as nephrogenic systemic fibrosis is avoided. As a proof of concept, an in vivo PET/MR study in mice is presented showing tumor targeting of Zr/Fe-DFO-micelles through the enhanced permeability and retention (EPR) effect of tumors, yielding high tumor-to-blood (10.3 ± 3.6) and tumor-to-muscle (15.3 ± 8.1) ratios at 48 h post injection. In vivo PET images clearly delineate the tumor tissue and show good correspondence with ex vivo biodistribution results. In vivo magnetic resonance imaging (MRI) allows visualization of the intratumoral distribution of the Zr/Fe-DFO-micelles at high resolution. In summary, the Zr/Fe-DFO-micelle nanoparticulate platform allows EPR-based tumor PET/MRI, and, furthermore, holds great potential for PET/MR image guided drug delivery.

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Section: Zirconium-89 Labeling Of Micelles : Labeling Of the Micellesmentioning

confidence: 99%

⁸⁹Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T₁‐Weighted MR Imaging

Starmans

Hummelink

Rossin

et al. 2015

Adv Healthcare Materials

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“…36,37 Previously, multiple simultaneous foci have been used for hyperthermia induced local drug delivery to enlarge the heated region as compared to a single static focus. 57 The current single focus sweep approach for MR-HIFU mediated mild hyperthermia, using rapid and sequential electronic steering of the ultrasound beam, 42,52,58 is a feasible and attractive heating strategy due to the efficient localized heating. However, this approach might also suffer from instantaneous, high, and localized acoustic pressures and intensities, leading to unfavorable mechanical effects and nonuniform and thus less controlled or less predictable heating in tissue.…”

Section: Discussionmentioning

confidence: 99%

Reduction of peak acoustic pressure and shaping of heated region by use of multifoci sonications in MR‐guided high‐intensity focused ultrasound mediated mild hyperthermia

et al. 2012

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Purpose: Ablative hyperthermia (>55• C) has been used as a definitive treatment for accessible solid tumors not amenable to surgery, whereas mild hyperthermia (40-45• C) has been shown effective as an adjuvant for both radiotherapy and chemotherapy. An optimal mild hyperthermia treatment is spatially accurate, with precise and homogeneous heating limited to the target region while also limiting the likelihood of unwanted thermal or mechanical bioeffects (tissue damage, vascular shutoff). Magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) can noninvasively heat solid tumors under image-guidance. In a mild hyperthermia setting, a sonication approach utilizing multiple concurrent foci may provide the benefit of reducing acoustic pressure in the focal region (leading to reduced or no mechanical effects), while providing better control over the heating. The objective of this study was to design, implement, and characterize a multifoci sonication approach in combination with a mild hyperthermia heating algorithm, and compare it to the more conventional method of electronically sweeping a single focus. Methods: Simulations (acoustic and thermal) and measurements (acoustic, with needle hydrophone) were performed. In addition, heating performance of multifoci and single focus sonications was compared using a clinical MR-HIFU platform in a phantom (target = 4-16 mm), in normal rabbit thigh muscle (target = 8 mm), and in a Vx2 tumor (target = 8 mm). A binary control algorithm was used for real-time mild hyperthermia feedback control (target range = 40.5-41• C). Data were analyzed for peak acoustic pressure and intensity, heating energy efficiency, temperature accuracy (mean), homogeneity of heating (standard deviation [SD], T10 and T90), diameter and length of the heated region, and thermal dose (CEM 43 ). Results: Compared to the single focus approach, multifoci sonications showed significantly lower (67% reduction) peak acoustic pressures in simulations and hydrophone measurements. In a rabbit Vx2 tumor, both single focus and multifoci heating approaches were accurate (mean = 40.82±0.12• C [single] and 40.70±0.09) and precise (standard deviation = 0.65±0.05• C [single] and 0.64±0.04, producing homogeneous heating (T 10-90 = 1.62• C [single] and 1.41. Heated regions were significantly shorter in the beam path direction (35% reduction, p < 0.05, Tukey) for multifoci sonications, i.e., resulting in an aspect ratio closer to one. Energy efficiency was lower for the multifoci approach. Similar results were achieved in phantom and rabbit muscle heating experiments. Conclusions: A multifoci sonication approach was combined with a mild hyperthermia heating algorithm, and implemented on a clinical MR-HIFU platform. This approach resulted in accurate and precise heating within the targeted region with significantly lower acoustic pressures and spatially more confined heating in the beam path direction compared to the single focus sonication method. The reduction in acoustic pressure and improvement in sp...

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“…Dedicated hybrid systems have already been introduced into clinical applications. 15,78,79 Localized drug release from TSL has been demonstrated in rodents, 55,80 and nonrodents, [81][82][83] using MRI for the control of hyperthermia. Beyond controlling the volume of heating, encapsulation of MRI contrast agents in TSL formulations allows additional characterization of the drug delivery only accessible in humans when using MRI.…”

Section: Thermosensitive Liposomes For Mri-guided Drug Deliverymentioning

confidence: 99%

Thermosensitive liposomal drug delivery systems: state of the art review

Kneidl¹,

Peller²,

Winter³

et al. 2014

IJN

145

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Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine.

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Tumour hyperthermia and ablation in rats using a clinical MR‐HIFU system equipped with a dedicated small animal set‐up

Cited by 70 publications

References 48 publications

⁸⁹Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T₁‐Weighted MR Imaging

⁸⁹Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T₁‐Weighted MR Imaging

Reduction of peak acoustic pressure and shaping of heated region by use of multifoci sonications in MR‐guided high‐intensity focused ultrasound mediated mild hyperthermia

Thermosensitive liposomal drug delivery systems: state of the art review

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Tumour hyperthermia and ablation in rats using a clinical MR‐HIFU system equipped with a dedicated small animal set‐up

Cited by 70 publications

References 48 publications

89Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T1‐Weighted MR Imaging

89Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T1‐Weighted MR Imaging

Reduction of peak acoustic pressure and shaping of heated region by use of multifoci sonications in MR‐guided high‐intensity focused ultrasound mediated mild hyperthermia

Thermosensitive liposomal drug delivery systems: state of the art review

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⁸⁹Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T₁‐Weighted MR Imaging

⁸⁹Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T₁‐Weighted MR Imaging