Percutaneous ultrasound guided PEG-coated gold nanoparticles enhanced radiofrequency ablation in liver

AbstractTo investigate the effects of PEG-coated gold nanoparticles on ablation zone volumes following in vivo radiofrequency ablation of porcine liver. This prospective study was performed following institutional animal care and committee approval was used. Radiofrequency ablations were performed in the livers of ten Sus scrofa domesticus swines. During each ablation, 10 mL (mL) of Peg-coated gold nanoparticles at two different concentrations (0.5 mg/mL and 0.01 mg/mL) were injected through the electrode channel into the target zone. For the control group, 10 mL of physiological saline was used. Five to ten minutes after each ablation, contrast enhanced ultrasound (CEUS) was performed to evaluate the volume of the coagulation zone. On day five we performed another CEUS and the animals were sacrificed. Treated tissues were explanted for quantification of the ablation zones’ volumes. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. A total of 30 ablations were performed in the livers. The mean coagulation zone volume as measured by CEUS on day 5 after RFA was: 21.69 ± 3.39 cm3, 19.22 ± 5.77 cm3, and 8.80 ± 3.33 cm3 for N1, N2 and PS respectively. The coagulation zone volume after N1 and N2 treatments was significantly higher compared to PS treatment (p < 0.001 and p = 0.025 respectively). There was no difference between N1 and N2 treatment (p = 0.60). In our proof-of concept, pilot study we have shown for the first time that when injected directly into the target tissue during RFA, gold nanoparticles can substantially increase the coagulation zone.

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Surface Adsorption of the Alpha-Emitter Astatine-211 to Gold Nanoparticles Is Stable In Vivo and Potentially Useful in Radionuclide Therapy

Journal of Nanotheranostics ◽

10.3390/jnt2040012 ◽

2021 ◽

Vol 2 (4) ◽

pp. 196-207

Author(s):

Emanuel Sporer ◽

Christian B. M. Poulie ◽

Sture Lindegren ◽

Emma Aneheim ◽

Holger Jensen ◽

...

Keyword(s):

Gold Nanoparticles ◽

Surface Adsorption ◽

Radiochemical Yield ◽

Gold Surface ◽

Mouse Serum ◽

Control Group ◽

Alpha Emitter ◽

Before And After ◽

The Stability

Targeted α-therapy (TAT) can eradicate tumor metastases while limiting overall toxicity. One of the most promising α-particle emitters is astatine-211 (211At). However, 211At-carbon bonds are notoriously unstable in vivo and no chelators are available. This hampers its adoption in TAT. In this study, the stability of 211At on the surface of gold nanoparticles (AuNPs) was investigated. The employed AuNPs had sizes in the 25–50 nm range. Radiolabeling by non-specific surface-adsorption in >99% radiochemical yield was achieved by mixing 211At and AuNPs both before and after polyethylene glycol (PEG) coating. The resulting 211At-AuNPs were first challenged by harsh oxidation with sodium hypochlorite, removing roughly 50% of the attached 211At. Second, incubation in mouse serum followed by a customized stability test, showed a stability of >95% after 4 h in serum. This high stability was further confirmed in an in vivo study, with comparison to a control group of free 211At. The AuNP-associated 211At showed low uptake in stomach and thyroid, which are hallmark organs of uptake of free 211At, combined with long circulation and high liver and spleen uptake, consistent with nanoparticle biodistribution. These results support that gold surface-adsorbed 211At has high biological stability and is a potentially useful delivery system in TAT.

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Microarray Gene Expression Analysis of Murine Tumor Heterogeneity Defined by Dynamic Contrast-Enhanced MRI

Molecular Imaging ◽

10.1162/15353500200202124 ◽

2002 ◽

Vol 1 (3) ◽

pp. 153535002002021

Author(s):

Nick G. Costouros ◽

Dominique Lorang ◽

Yantian Zhang ◽

Marshall S. Miller ◽

Felix E. Diehn ◽

...

Keyword(s):

Ribosomal Proteins ◽

Tumor Heterogeneity ◽

Protein Translation ◽

Pharmacokinetic Parameters ◽

Transcriptional Level ◽

Target Tissue ◽

Dce Mri ◽

Dynamic Contrast Enhanced ◽

Contrast Enhanced

Current methods of studying angiogenesis are limited in their ability to serially evaluate in vivo function throughout a target tissue. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and pharmacokinetic modeling provide a useful method for evaluating tissue vasculature based on contrast accumulation and washout. While it is often assumed that areas of high contrast enhancement and washout comprise areas of increased angiogenesis and tumor activity, the actual molecular pathways that are active in such areas are poorly understood. Using DCE-MRI in a murine subcutaneous tumor model, we were able to perform pharmacokinetic functional analysis of a tumor, coregistration of MRI images with histological cross-sections, immunohistochemistry, laser capture microdissection, and genetic profiling of tumor heterogeneity based on pharmacokinetic parameters. Using imaging as a template for biologic investigation, we have not found evidence of increased expression of proangiogenic modulators at the transcriptional level in either distinct pharmacokinetic region. Furthermore, these regions show no difference on histology and CD31 immunohistochemistry. However, the expression of ribosomal proteins was greatly increased in high enhancement and washout regions, implying increased protein translation and consequent increased cellular activity. Together, these findings point to the potential importance of posttranscriptional regulation in angiogenesis and the need for the development of angiogenesis-specific contrast agents to evaluate in vivo angiogenesis at a molecular level.

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Identification of androgen receptor phosphorylation in the primate ovary in vivo

Reproduction ◽

10.1530/rep-10-0140 ◽

2010 ◽

Vol 140 (1) ◽

pp. 93-104 ◽

Cited By ~ 11

Author(s):

Iain J McEwan ◽

Dagmara McGuinness ◽

Colin W Hay ◽

Robert P Millar ◽

Philippa T K Saunders ◽

...

Keyword(s):

Endothelial Cells ◽

Androgen Receptor ◽

Granulosa Cells ◽

Gnrh Antagonist ◽

Follicular Phase ◽

Surface Epithelium ◽

Control Group ◽

Target Tissue ◽

Receptor Phosphorylation

The androgen receptor (AR) is a member of the nuclear receptor superfamily, and is important for both male and female reproductive health. The receptor is a target for a number of post-translational modifications including phosphorylation, which has been intensively studied in vitro. However, little is known about the phosphorylation status of the receptor in target tissues in vivo. The common marmoset is a useful model for studying human reproductive functions, and comparison of the AR primary sequence from this primate shows high conservation of serines known to be phosphorylated in the human receptor and corresponding flanking amino acids. We have used a panel of phosphospecific antibodies to study AR phosphorylation in the marmoset ovary throughout the follicular phase and after treatment with GNRH antagonist or testosterone propionate. In normal follicular phase ovaries, total AR (both phosphorylated and non-phosphorylated forms) immunopositive staining was observed in several cell types including granulosa cells of developing follicles, theca cells and endothelial cells lining blood vessels. Receptor phosphorylation at serines 81, 308, and 650 was detected primarily in the granulosa cells of developing follicles, surface epithelium, and vessel endothelial cells. Testosterone treatment lead to a modest increase in AR staining in all stages of follicle studied, while GNRH antagonist had no effect. Neither treatment significantly altered the pattern of phosphorylation compared to the control group. These results demonstrate that phosphorylation of the AR occurs, at a subset of serine residues, in a reproductive target tissue in vivo, which appears refractory to hormonal manipulations.

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Electro-physiological parameters of hepatic radiofrequency ablation—a comparison of an in vitro versus an in vivo porcine liver model

Langenbeck s Archives of Surgery ◽

10.1007/s00423-009-0475-y ◽

2009 ◽

Vol 394 (3) ◽

pp. 503-509 ◽

Cited By ~ 5

Author(s):

R. Wahba ◽

C. Bangard ◽

R. Kleinert ◽

S. Rösgen ◽

J.-H. Fischer ◽

...

Keyword(s):

Radiofrequency Ablation ◽

Physiological Parameters ◽

Porcine Liver ◽

Liver Model

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Bipolar Saline-enhanced Electrode for Radiofrequency Ablation: Results of Experimental Study of in Vivo Porcine Liver

Radiology ◽

10.1148/radiol.2292020978 ◽

2003 ◽

Vol 229 (2) ◽

pp. 447-456 ◽

Cited By ~ 54

Author(s):

Fernando Burdío ◽

Antonio Güemes ◽

José M. Burdío ◽

Ana Navarro ◽

Ramón Sousa ◽

...

Keyword(s):

Experimental Study ◽

Radiofrequency Ablation ◽

Porcine Liver

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Efficient and facile delivery of gold nanoparticles in vivo using dissolvable microneedles for contrast-enhanced optical coherence tomography

Biomedical Optics Express ◽

10.1364/boe.1.000106 ◽

2010 ◽

Vol 1 (1) ◽

pp. 106 ◽

Cited By ~ 17

Author(s):

Chang Soo Kim ◽

Yeh-Chan Ahn ◽

Petra Wilder-Smith ◽

Seajin Oh ◽

Zhongping Chen ◽

...

Keyword(s):

Gold Nanoparticles ◽

Optical Coherence Tomography ◽

Optical Coherence ◽

Contrast Enhanced

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EXPERIMENTAL INVESTIGATION ON CARBACETAM INFLUENCE ON HYPOTHALAMUS TISSUE IN BRAIN INJURY

Medical Science of Ukraine (MSU) ◽

10.32345/2664-4738.1-2.2018.02 ◽

2018 ◽

Vol 14 (1-2) ◽

pp. 11-17

Author(s):

S.V. Ziablytsev ◽

T.I. Panova ◽

O.O. Starodubska ◽

O.O. Dyadik

Keyword(s):

Brain Injury ◽

Physiological Saline ◽

Neuroendocrine Cells ◽

Nerve Tissue ◽

Male Rats ◽

Control Group ◽

S 100 ◽

Hypothalamic Tissue ◽

Hematoxylin And Eosin ◽

The Brain

Relevance. A key role in the pathogenesis of the brain injury is played by destructive changes in the hypothalamus neuroendocrine cells. For the correction of such disorders, promising is carbacetam, which has antihypoxic, anti-edema and anti-shock effects. Objective: to investigate the effect of carbacetam on the processes of neurodegeneration in the paraventricular and supraoptical nuclei of the hypothalamus in the experimental brain injury. Material and methods. Brain injury were modeled on the V.M. Elskyy &S.V. Ziablitsev model on white non-breeding male rats weighing 200±10 g. Experimental animals (n=10) received intraabdominal injection of carbacetam at a dose of 5 mg/kg in 1 ml of physiological saline during the seven days after injury. In the control group (n=10), 1 ml of physiological saline was injected. Hypothalamic tissue microparticles performed a morphological and immunohistochemical evaluation of neurodegenerative changes when stained with hematoxylin and eosin and immunohistochemically to detect NSE, S-100 and GFAP neuromarkers. Results. Carbacetam reduced the degenerative processes in the nervous tissue of the paraventricular and supraoptical nuclei of the hypothalamus, which was manifested by the restoration of normal morphological features, in contrast to rats that did not receive the drug. Immunohistochemically, GFAP and S-100 glial markers exhibited reduced, reflecting a reduction in degenerative changes in the nerve tissue. Expressions of the neurons marker NSE increased, reflecting high metabolic activity of the neurons. Conclusions. Revealed changes in the expression of markers of neurons and glia showed a restoration of normal neuronal activity due to the introduction of carbacetam.

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Pilot in vivo studies on transcutaneous boiling histotripsy in porcine liver and kidney

Scientific Reports ◽

10.1038/s41598-019-56658-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Tatiana D. Khokhlova ◽

George R. Schade ◽

Yak-Nam Wang ◽

Sergey V. Buravkov ◽

Valeriy P. Chernikov ◽

...

Keyword(s):

Peak Power ◽

Ex Vivo ◽

Respiratory Gating ◽

Subcutaneous Fat ◽

High Intensity Focused Ultrasound ◽

In Vivo Studies ◽

Swine Model ◽

Target Tissue ◽

Porcine Liver

AbstractBoiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks. BH treatments with real-time ultrasound (US) guidance allowed by BH-generated bubbles were previously demonstrated ex vivo and in vivo in exposed porcine liver and small animals. Here, the feasibility of US-guided transabdominal and partially transcostal BH ablation of kidney and liver in an acute in vivo swine model was evaluated for 6 animals. BH parameters were: 1.5 MHz frequency, 5–30 pulses of 1–10 ms duration per focus, 1% duty cycle, peak acoustic powers 0.9–3.8 kW, sonication foci spaced 1–1.5 mm apart in a rectangular grid with 5–15 mm linear dimensions. In kidneys, well-demarcated volumetric BH lesions were generated without respiratory gating and renal medulla and collecting system were more resistant to BH than cortex. The treatment was accelerated 10-fold by using shorter BH pulses of larger peak power without affecting the quality of tissue fractionation. In liver, respiratory motion and aberrations from subcutaneous fat affected the treatment but increasing the peak power provided successful lesion generation. These data indicate BH is a promising technology for transabdominal and transcostal mechanical ablation of tumors in kidney and liver.

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63 EQUINE FOLLICLES MODULATE CORTISOL LEVELS AND CAPABILITY OF OOCYTES TO ADAPT TO STRESS SITUATIONS

Reproduction Fertility and Development ◽

10.1071/rdv28n2ab63 ◽

2016 ◽

Vol 28 (2) ◽

pp. 161

Author(s):

D. Scarlet ◽

N. Ille ◽

G. D. A. Gastal ◽

B. G. Alves ◽

S. O. Paiva ◽

...

Keyword(s):

Pearson Correlation ◽

Plasma Concentrations ◽

Reproductive Function ◽

Control Group ◽

Target Tissue ◽

Preovulatory Follicles ◽

Before And After ◽

Cortisol Levels ◽

Systemic Stress

Glucocorticoids are mediators of the systemic stress response. Acute or chronic stress characterised by high cortisol concentrations in the periphery impairs reproductive function in a variety of species and therefore may affect fertility. The ovary has been shown to be a target tissue for glucocorticoids in many species, including the mare. This study hypothesised that the equine ovary possesses internal mechanisms to modulate cortisol activity and that supraphysiologic levels of glucocorticoids do not affect oocyte IVM rates. Light horse mares (n = 9) were used in this study. Growing follicles from an induced follicular wave were divided into the following groups: G1: 5–9 mm, G2: 10–14 mm, G3: 15–19 mm, G4: 20–24 mm, and G5: ≥25 mm. Follicular fluid (FF) and compact cumulus‐oocyte complexes (COCs) were obtained by ultrasound-guided transvaginal aspiration. Blood samples were collected at the beginning and the end of every aspiration session. Cortisol (DE1887, Demeditec, Kiel-Wellsee, Germany), progesterone (ADI-901–011, Enzo Life Sciences, Farmingdale, NY, USA), and corticosteroid binding globulin (CBG, MBS047353, MyBioSource, San Diego, CA, USA) concentrations were determined by ELISA. COCs (n = 80) were randomly distributed to either the control group (DMEM-F12+ medium) or the following hydrocortisone treatment groups: 0.1 µg mL–1, 1 µg mL–1, 5 µg mL–1, 10 µg mL–1. Maturation rate was assessed 30 h after incubation. Statistical analysis was performed with the SPSS Statistics 22 software. Data were analysed using one-way ANOVA, Pearson correlation, and chi-squared test. Cortisol (115.4 ± 13.3 ng mL–1) and progesterone (22.1 ± 3.1 ng mL–1) FF concentrations were higher (P < 0.05) in G5 follicles than in all other groups, and were positively correlated (r = 0.8; P < 0.001). Plasma concentrations of cortisol (118.6 ± 7.8 v. 120.3 ± 12.2 ng mL–1), progesterone (2.4 ± 0.5 v. 2.5 ± 0.4 ng mL–1), and CBG (11.1 ± 5.1 v. 9.9 ± 3.2 µg mL–1) did not differ before and after follicle aspiration. However, plasma CBG and progesterone were negatively correlated (r = –0.56; P < 0.01). Maturation rates did not differ among groups, regardless of the hydrocortisone concentration added to the culture medium. Our results demonstrated higher cortisol concentrations in preovulatory follicles in vivo, suggesting its importance for oocyte maturation. The greater unbound cortisol available in the FF of preovulatory follicles can be indicative of the displacement of cortisol from CBG in favour of progesterone. Furthermore, equine oocytes were capable of surviving cortisol concentrations 100 times higher than those physiologically present in preovulatory follicles. This finding suggests the ability of equine oocytes to modulate cortisol levels and adapt to stress situations.

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