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Gas-filled phospholipid nanoparticles conjugated with gadolinium play a role as a potential theragnostics for MR-guided HIFU ablation.

ABSTRACT: To develop a long-circulating theragnostics, meaning therapeutics and diagnostics for MR-guided HIFU ablation, we designed and prepared Gd-C(5)F(12)-phospholipid nanobubbles (PLNs) 30-100 nm in diameter. The biochemical and physical characterization of Gd-C(5)F(12)-PLNs were performed. Since Gd-C(5)F(12)-PLN-50 (??=?50 nm) and Gd-C(5)F(12)-PLN-100 (??=?100 nm) enhanced the hyperthermal effect of HIFU size- and concentration-dependently in a tissue-mimicking phantom, its circulation, distribution, tumor accumulation and tumor ablation were examined in tumor-bearing mice. The plasma-half life of Gd-C(5)F(12)-PLNs was longer than 1.5 hrs. Gd-C(5)F(12)-PLNs mainly accumulated in the liver and the spleen, suggesting that they are slowly secreted through the hepatobiliary pathway. Monitored by the T1 signal intensity of MR, Gd-C(5)F(12)-PLNs accumulated in tumor tissues for 8 hours in mice. HIFU with Gd-C(5)F(12)-PLN-100 showed the increased tumor ablation area as compared with HIFU alone. The results suggest that Gd-C(5)F(12)-PLNs exhibit a potential theragnostics for MR-guided HIFU ablation.

SUBMITTER: Choi SY

PROVIDER: S-EPMC3315537 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Gas-filled phospholipid nanoparticles conjugated with gadolinium play a role as a potential theragnostics for MR-guided HIFU ablation.

Choi Se-Young SY Kim Young-Sun YS Seo Yeong-Ju YJ Yang Jehoon J Choi Kyu-Sil KS

PloS one 20120329 3

To develop a long-circulating theragnostics, meaning therapeutics and diagnostics for MR-guided HIFU ablation, we designed and prepared Gd-C(5)F(12)-phospholipid nanobubbles (PLNs) 30-100 nm in diameter. The biochemical and physical characterization of Gd-C(5)F(12)-PLNs were performed. Since Gd-C(5)F(12)-PLN-50 (Φ = 50 nm) and Gd-C(5)F(12)-PLN-100 (Φ = 100 nm) enhanced the hyperthermal effect of HIFU size- and concentration-dependently in a tissue-mimicking phantom, its circulation, distribution ...[more]

PMID: 22479602

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Project description:PurposeUltrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system.MethodsVolumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160-300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson's trichrome and toluidine blue staining.ResultsAll targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation.ConclusionOur preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post-treatment verification of thermal lesions without contrast injection.

Project description:Feasibility of targeted and volumetric hyperthermia (40-45 °C) delivery to the prostate with a commercial MR-guided endorectal ultrasound phased array system, designed specifically for thermal ablation and approved for ablation trials (ExAblate 2100, Insightec Ltd.), was assessed through computer simulations and tissue-equivalent phantom experiments with the intention of fast clinical translation for targeted hyperthermia in conjunction with radiotherapy and chemotherapy.The simulations included a 3D finite element method based biothermal model, and acoustic field calculations for the ExAblate ERUS phased array (2.3 MHz, 2.3 × 4.0 cm(2), ∼1000 channels) using the rectangular radiator method. Array beamforming strategies were investigated to deliver protracted, continuous-wave hyperthermia to focal prostate cancer targets identified from representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Preliminary experiments included beamformed sonications in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W).Acoustic intensities considered during simulation were limited to ensure mild hyperthermia (Tmax < 45 °C) and fail-safe operation of the ExAblate array (spatial and time averaged acoustic intensity ISATA < 3.4 W/cm(2)). Tissue volumes with therapeutic temperature levels (T > 41 °C) were estimated. Numerical simulations indicated that T > 41 °C was calculated in 13-23 cm(3) volumes for sonications with planar or diverging beam patterns at 0.9-1.2 W/cm(2), in 4.5-5.8 cm(3) volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm(2), and in ∼6.0 cm(3) for curvilinear (cylindrical) beam patterns at 0.75 W/cm(2). Focused heating patterns may be practical for treating focal disease in a single posterior quadrant of the prostate and diffused heating patterns may be useful for heating quadrants, hemigland volumes or even bilateral targets. Treatable volumes may be limited by pubic bone heating. Therapeutic temperatures were estimated for a range of physiological parameters, sonication duty cycles and rectal cooling. Hyperthermia specific phasing patterns were implemented on the ExAblate prostate array and continuous-wave sonications (∼0.88 W/cm(2), 15 min) were performed in tissue-mimicking material with real-time MR-based temperature imaging (PRFS imaging at 3.0 T). Shapes of heating patterns observed during experiments were consistent with simulations.The ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints.

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Gas-filled phospholipid nanoparticles conjugated with gadolinium play a role as a potential theragnostics for MR-guided HIFU ablation.

Publications

Gas-filled phospholipid nanoparticles conjugated with gadolinium play a role as a potential theragnostics for MR-guided HIFU ablation.

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