Optimal treatment occasion for ultrasound stimulated microbubbles in promoting gemcitabine delivery to VX2 tumors

Luo, Tingting; Bai, Luhua; Zhang, Yi; Huang, Leidan; Li, Hui; Gao, Shunji; Dong, Xiaoxiao; Li, Ningshan; Liu, Zheng

doi:10.1080/10717544.2022.2115163

Cited by 9 publications

(11 citation statements)

References 48 publications

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“…The optimal occasion of USMB treatment is a critical factor in uencing its synergistic therapeutic effect. Luo et al [27] demonstrated that the tumor drug concentration was highest in the USMB treatment group immediately after gemcitabine infusion, 2.83 times higher than that in the control group. The optimal timing for USMB treatment is immediately after the completion of chemotherapy drug infusion.…”

Section: Discussionmentioning

confidence: 97%

Clinical Study on Low-intensity Ultrasound Stimulated Microbubbles to Enhance Neoadjuvant Chemotherapy in Breast Cancer

Chen

Jin

Zhang

et al. 2023

Preprint

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Objective low-intensity ultrasound stimulated microbubbles (USMB), utilizing microbubble-assisted ultrasound cavitation, has the potential to enhance tumor blood perfusion and improve chemotherapy effectiveness. It has been shown to extend survival in pancreatic cancer patients. This study aims to explore the safety and efficacy of USMB in enhancing neoadjuvant chemotherapy(NAC) for breast cancer. Methods Seventeen breast cancer patients were randomly assigned to an experimental group (n = 10) and a control group (n = 7). The experimental group received USMB treatment within 1 hour after each NAC cycle, while the control group underwent ultrasound sham imaging. Adverse events were recorded for both groups. The objective response rate was defined as the percentage of patients who had a best-response rating of complete response (CR) or partial response (PR) confirmed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Tumor perfusion was analyzed through the time-intensity curve (TIC) before and after each USMB treatment, obtaining parameters such as peak enhancement (PE), wash-in area under the curve (WiAUC), wash-out area under the curve (WoAUC), and wash-in and wash-out area under the curve (WiWoAUC). This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2200056718). Results Three out of 17 patients were lost to follow-up. The comparison of adverse event rates between the two groups showed no statistically significant difference. According to the RECIST 1.1, in the experimental group, one subject achieved CR, five subjects achieved PR, and three subjects had stable disease (SD). In the control group, three subjects achieved PR and two subjects had SD. There was no statistically significant difference in the objective response rate (66.7% vs. 60%, p > 0.99). In the experimental group, the PE, WiAUC, WoAUC, and WiWoAUC of breast cancer showed a significant increase compared to pre-USMB treatment (p = 0.03, p = 0.01, p = 0.03, p < 0.01). Conclusions Low-intensity USMB treatment does not increase adverse events to NAC and improves blood perfusion in breast cancer. However, further large-sample, multicenter clinical studies are needed to evaluate the therapeutic efficacy of USMB treatment.

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Section: Discussionmentioning

confidence: 97%

Clinical Study on Low-intensity Ultrasound Stimulated Microbubbles to Enhance Neoadjuvant Chemotherapy in Breast Cancer

Chen

Jin

Zhang

et al. 2023

Preprint

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“…The PFP droplet emulsion was based on the lipid-coated microbubble Zhifuxian, which has been frequently used in previous studies. 23,30,32 The PFP droplets were encapsulated in a lipid membrane, similar to a US contrast agent, with a chemically stable dispersion. We did not consider the size distribution of the droplets because they were administered by local interventional injection rather than intravenous injection.…”

Section: Discussionmentioning

confidence: 99%

“…Compared to the large arrays of most histotripsies or boiling histotripsy, 8 our 35 mm transducer can easily find acoustic windows once guided by US imaging, and the low frequency of 596 kHz has better penetration. The PFP droplet emulsion was based on the lipid‐coated microbubble Zhifuxian, which has been frequently used in previous studies 23,30,32 . The PFP droplets were encapsulated in a lipid membrane, similar to a US contrast agent, with a chemically stable dispersion.…”

Section: Discussionmentioning

confidence: 99%

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A new sonoablation using acoustic droplet vaporization and focused ultrasound: A feasibility study

Li,

He,

Tang

et al. 2023

Medical Physics

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BackgroundHistotripsy and boiling histotripsy are two methods of mechanical ablation that use high‐pressure focused ultrasound (FUS).PurposeHere, a new bubble sonoablation technique was investigated using low‐pressure FUS in combination with local injection of perfluoropentane (PFP) in rabbit liver.MethodsFifteen healthy New Zealand white rabbits were treated with FUS alone, FUS + PFP or PFP alone. FUS was performed using a single‐element focused transducer (frequency 596 kHz, 0.27 ms pulses, 0.54% duty cycle, and peak negative pressure 2.0 MPa). Ten minutes before FUS treatment, the PFP droplet was locally injected into the rabbit liver, where the ultrasound was focused. Contrast‐enhanced ultrasound (CEUS) of the liver was performed, and the temperature at the liver surface in the targeted liver region was recorded during treatment. The livers were collected for pathological examination. Statistical significance was set at p < 0.05. Paired t‐tests were used to compare the pre‐ and post‐treatment values. One‐way analysis of variance was performed to compare multiple groups, and the least significant difference method was used for further comparisons between the two groups.ResultsAnalysis of CEUS data showed that the values of area under the curve (AUC) were significantly different in the PFP + FUS group pre‐ (10453.644 ± 1182.93) and post‐treatment (4058.098 ± 2720.41), and the AUC values of PFP + FUS post‐treatment (4058.098 ± 2720.41) were also significantly lower than those of the FUS (9946.694 ± 1071.54) and the PFP (10364.794 ± 2181.53) groups. The peak intensity values also showed the same results, the value of peak intensity of PFP+FUS post‐treatment was 82.958 ± 13.99, whereas there was no difference between FUS (106.61 ± 7.61) and PFP (104.136 ± 10.55). Hematoxylin and eosin (H&E) staining revealed that the pathological damage ratings of the PFP + FUS, PFP, and FUS groups were grade 3, grade 1, and grade 0, respectively. Specifically, the area of liver necrosis in the PFP + FUS group (0.99 ± 0.29 cm2) was 198 times higher than that in the PFP group (0.005 ± 0.008 cm2), whereas no necrosis was observed in the livers treated with FUS alone. Simultaneously, the number of vacuoles in the liver of the PFP + FUS group (35.50 ± 23.31) was approximately five times that of the PFP group (7.00 ± 12.88), whereas no vacuoles were found in the liver treated with FUS alone.ConclusionPFP droplets combined with FUS can destroy liver tissue and cause tissue necrosis in the droplet injection area, without affecting the structure of surrounding tissue.

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“…Other studies 6,7 have shown that when the relevant parameters of ultrasonic diagnostic instrument are adjusted, USMB can produce steady-state cavitation, which has the effect of temporarily increasing local blood perfusion and increasing the osmotic release of drugs in local tissues. This technology has been widely used in the basic research of tumor chemotherapy and can enhance the effect of tumor chemotherapy 8,9 .…”

Section: Introductionmentioning

confidence: 99%

Ultrasound stimulated microbubbles cavitation enhanced the therapeutic effect of colchicine in rats with acute gouty arthritis

Zhang,

Bo,

Wang

et al. 2024

Preprint

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Objective To investigate whether cavitation induced by ultrasound stimulated microbubbles (USMB) can enhance the therapeutic effect of colchicine and reduce its side effects on acute gouty arthritis (AGA) in rats. Materials and Methods Each rat underwent right ankle joint contrast-enhanced ultrasound (CEUS) before and following cavitation treatment. The area under the curve (AUC) of CEUS before and after cavitation and among groups were compared to contrast the impact on blood perfusion of the ankle joint in rats with cavitation. The symptoms of AGA were evaluated based on 24-hour ankle joint swelling degree and gait score. The infiltration of neutrophils was assessed using the Hematoxylin-eosin(HE)staining, while the inflammation and dilation of blood vessels were measured by and plasma interleukin-1β (IL-1β) and endothelial nitric oxide synthase (eNOS). Moreover, the magnitude of side effects was analyzed by gastrointestinal reaction score. Results The AUC after cavitation induced by USMB were significantly higher than those before cavitation. When compared with groups without cavitation, the AUC were markedly higher in groups treated with cavitation (all p<0.01). In groups treated with cavitation combined with colchicine, the degree of ankle swelling, gait scores, and the level of plasma IL-1β in AGA rats were lower, while the concentration of plasma eNOS was higher, group treated with colchicine alone (all p<0.05). HE staining showed that cavitation combined with colchicine helped to reduce the neutrophil synovial infiltration of ankle joint and decrease the gastrointestinal reaction score in rats with AGA. Compared with the three groups receiving drug treatment, the incidence of gastrointestinal reaction score in the low concentration group was significantly lower than that in the high concentration groups (all p<0.05). Conclusion The cavitation induced by USMB could significantly enhance the blood perfusion of ankle joint in rats with AGA, leading to the increase in therapeutic effect of colchicine and reduce the dose used of colchicine, thus minimizing the side effects associated with it.

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Optimal treatment occasion for ultrasound stimulated microbubbles in promoting gemcitabine delivery to VX2 tumors

Cited by 9 publications

References 48 publications

Clinical Study on Low-intensity Ultrasound Stimulated Microbubbles to Enhance Neoadjuvant Chemotherapy in Breast Cancer

Clinical Study on Low-intensity Ultrasound Stimulated Microbubbles to Enhance Neoadjuvant Chemotherapy in Breast Cancer

A new sonoablation using acoustic droplet vaporization and focused ultrasound: A feasibility study

Ultrasound stimulated microbubbles cavitation enhanced the therapeutic effect of colchicine in rats with acute gouty arthritis

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