Using imaging modalities to predict nanoparticle distribution and treatment efficacy in solid tumors: The growing role of ultrasound.

Michaela B Cooley, Dana Wegierak, Agata A Exner
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Abstract

Nanomedicine in oncology has not had the success in clinical impact that was anticipated in the early stages of the field's development. Ideally, nanomedicines selectively accumulate in tumor tissue and reduce systemic side effects compared to traditional chemotherapeutics. However, this has been more successful in preclinical animal models than in humans. The causes of this failure to translate may be related to the intra- and inter-patient heterogeneity of the tumor microenvironment. Predicting whether a patient will respond positively to treatment prior to its initiation, through evaluation of characteristics like nanoparticle extravasation and retention potential in the tumor, may be a way to improve nanomedicine success rate. While there are many potential strategies to accomplish this, prediction and patient stratification via noninvasive medical imaging may be the most efficient and specific strategy. There have been some preclinical and clinical advances in this area using MRI, CT, PET, and other modalities. An alternative approach that has not been studied as extensively is biomedical ultrasound, including techniques such as multiparametric contrast-enhanced ultrasound (mpCEUS), doppler, elastography, and super-resolution processing. Ultrasound is safe, inexpensive, noninvasive, and capable of imaging the entire tumor with high temporal and spatial resolution. In this work, we summarize the in vivo imaging tools that have been used to predict nanoparticle distribution and treatment efficacy in oncology. We emphasize ultrasound imaging and the recent developments in the field concerning CEUS. The successful implementation of an imaging strategy for prediction of nanoparticle accumulation in tumors could lead to increased clinical translation of nanomedicines, and subsequently, improved patient outcomes. This article is categorized under: Diagnostic Tools In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery Emerging Technologies.

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利用成像模式预测纳米粒子在实体瘤中的分布和治疗效果:超声的作用越来越大。
纳米药物在肿瘤学领域的临床效果并没有达到该领域发展初期的预期。理想情况下,纳米药物会选择性地积聚在肿瘤组织中,与传统化疗药物相比,可减少全身副作用。然而,这在临床前动物模型中比在人体中更为成功。未能转化的原因可能与肿瘤微环境在患者体内和患者之间的异质性有关。通过评估纳米粒子的外渗和在肿瘤中的滞留潜力等特性,在开始治疗前预测患者是否会对治疗产生积极反应,可能是提高纳米药物成功率的一种方法。虽然有许多潜在的策略可以实现这一目标,但通过无创医学成像进行预测和患者分层可能是最有效、最具体的策略。在这一领域,利用核磁共振成像、CT、正电子发射计算机断层扫描和其他模式已经取得了一些临床前和临床上的进展。另一种尚未得到广泛研究的方法是生物医学超声,包括多参数对比增强超声(mpCEUS)、多普勒、弹性成像和超分辨率处理等技术。超声波安全、廉价、无创,能够以较高的时间和空间分辨率对整个肿瘤进行成像。在这项工作中,我们总结了用于预测纳米粒子分布和肿瘤治疗效果的体内成像工具。我们强调超声成像和 CEUS 领域的最新进展。成功实施用于预测纳米粒子在肿瘤中积累的成像策略可促进纳米药物的临床转化,从而改善患者的预后。本文归类于诊断工具 体内纳米诊断和成像 治疗方法和药物发现 用于肿瘤疾病的纳米药物 治疗方法和药物发现 新兴技术。
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