肿瘤异质性的影像学定量分析进展

对影像学指标定量分析肿瘤异质性及其研究进展进行了综述.阐述了目前在肿瘤异质性定量分析研究中常用的影像学指标在正电子发射体层显像(PET)和磁共振成像(MRI)等不同成像技术中的应用,分析其在临床预测肿瘤患者放化疗疗效或生存期等方面的价值.临床研究结果显示,异质性参数与患者放化疗疗效、生存期等存在显著相关性,具有一定的临床参考价值.综合不同影像的异质性参数以寻求最优的参数来评价肿瘤异质性可完善量化分析肿瘤异质性的标准.     

骨肉瘤的缺氧微环境与放疗增敏进展

放疗是恶性肿瘤重要的辅助治疗手段,但骨肉瘤对放疗不是十分敏感,存在一定的放疗抵抗。即相对于对放射线敏感的肿瘤(如视网膜母细胞瘤、鼻咽癌、卵巢癌中的无性细胞瘤、睾丸精原细胞瘤、肾胚胎瘤、恶性淋巴瘤等)来讲,同等或更大的放射剂量也难以达到敏感肿瘤所能有的局部控制率。许多研究表明,低剂量分次放疗(2 Gy/次,共60 Gy)的5年局部控制率为40%～68%,但5年的局部控制率和生存率并没有相关性。近几年,骨肉瘤具有固有的放疗抵抗性的概念已经受到多项研究的质疑,有的骨肉瘤的放疗效果要好于黑色素瘤,而黑色素瘤是公认的放疗抵抗肿瘤。此外,若采取大分割治疗(总量不变,提高每次的放疗剂量),虽然骨肉瘤对普通X射线不算敏感,但其对质子和重离子治疗应答率明显提高。因此选择适当的患者、采取合适的放疗方法可以提高放疗效果。放疗抵抗的直接原因是肿瘤细胞对DNA损伤的修复能力和耐受能力,这和肿瘤的异质性有关。许多研究表明低氧微环境是放疗抵抗最重要的环境因素。首先,缺氧微环境为肿瘤细胞产生放疗抵抗提供重要的发生条件,缺氧微环境刺激细胞产生低氧诱导因子(Hypoxia inducible factors,HIF),缺氧预处理可增加骨肉瘤细胞的放疗抵抗,缺氧诱导因子(HIF-1、HIF-2)、自噬相关因子(LC3-Ⅱ)在骨肉瘤组织中高表达,若敲除HIF基因后,细胞自噬水平和凋亡显著升高,但抑制自噬后,细胞凋亡并没有减少,说明细胞在缺氧微环境中主要通过HIF实现放化疗抵抗。放疗后DNA损伤的修复能力也是放疗抵抗的机制之一,通过长时间监测DNA损伤的修复蛋白γ-H2AX和53BP1,即可评估DNA损伤的修复情况。针对引起放疗抵抗的原因,改变肿瘤缺氧微环境是放疗增敏的有效手段,主要有增加氧供应和研究靶向缺氧细胞的化学增敏药物。高压氧舱可提供高压氧环境,直接增加肿瘤组织的含氧量,但患者依从性较差,增敏效果不确切。结合尼克酰胺(针对急性缺氧)与慢性缺氧改良剂(如O_2和CO_2气体的混合物)可明显改善肿瘤组织的急慢性缺氧环境,从而增强放疗的效果。此外,有人提出热疗是克服放疗抵抗、增加放疗敏感性的有效方法,研究证明放疗同时把瘤组织加热到43℃可显著提高放疗效果。未来,骨肉瘤的放疗将在放疗增敏研究的基础上,结合立体定向放疗、质子放疗和重离子放疗等先进技术手段,低剂量、高精准,和手术治疗及化疗有机结合,实现更好的治疗效果。     

HIFU治疗裸鼠皮下移植瘤超声和磁共振变化的初步观察

目的初步探讨高强度聚焦超声对裸鼠卵巢癌皮下移植瘤治疗前后的超声和磁共振变化.方法HIFU治疗裸鼠卵巢癌模型12例,高强度聚焦超声治疗肿瘤外侧1/2,治疗前后进行超声和磁共振检查.结果(1)治疗前肿瘤组织超声表现为低回声,彩色和能量多普勒检测肿瘤内部及周边均有少许血流信号;治疗后肿瘤组织回声增强,彩色和能量多普勒检测肿瘤治疗区域内部及周边均无血流信号.(2)磁共振检查治疗区域肿瘤组织增强后未见明显强化.结论HIFU能准确破坏卵巢肿瘤,治疗过程中超声定位准确、方便,治疗后磁共振有助于评价其疗效,为临床应用提供实验依据.     

吸氧性PET果汁饮料瓶的制备及性能研究

将吸氧剂与聚对苯二甲酸乙二醇酯(PET)共混制得吸氧性PET橙汁饮料瓶。利用扫描电子显微镜、容器透氧仪对共混材料的结构与性能进行测定;利用高效液相色谱和色差仪对瓶装橙汁的质量进行检测。结果表明,吸氧剂能有效提高PET瓶的阻氧性能,减缓橙汁中维生素C的氧化速度,保证其色泽鲜亮,口感纯正。     

18F-FDG PET图像中肿瘤非均匀性评估模型

肿瘤在功能图像中表现出的非均匀特性能够一定程度上反应出其基本特性和对治疗的响应,对这一特性的数学描述和建模可为治疗和预估治疗效果提供有意义的量化参考数据.本文提出一种新的放射性同位素氟18标记的脱氧葡萄糖(18F-FDG)正电子发射断层影像(PET)中肿瘤内部非均匀性计算模型,通过图像中相邻像素的FDG标准摄取值(SUV)差异和其位置特征,可得出能描述肿瘤图像呈现的非均匀特性的参数H指数.使用矩形和高斯球模体以及3例肺癌患者数据,通过与灰度共生矩阵(GLCM)图像分析法比较研究,验证了该模型的有效性.     

红外热成像技术研究聚酯纤维的冷拉现象

采用红外热成像技术研究了聚酯(PET)纤维的冷拉颈缩现象,选用一种特殊的18μm微焦镜头,形变过程中纤维的温度和直径变化能被同时检测到。红外热像图显示冷拉生热温度变化仅发生在纤维成颈区域,而且随着拉伸速率的提高,成颈区域温度升高可超过环境温度50℃~85℃。通过热力学的方法分析形变过程内能的变化,结果发现,内能随着拉伸不断减小,显示PET纤维在形变过程引发诱导结晶。     

红外热成像技术研究聚酯纤维的冷拉现象EI北大核心CSCD

采用红外热成像技术研究了聚酯（PET）纤维的冷拉颈缩现象,选用一种特殊的18μm微焦镜头,形变过程中纤维的温度和直径变化能被同时检测到。红外热像图显示冷拉生热温度变化仅发生在纤维成颈区域,而且随着拉伸速率的提高,成颈区域温度升高可超过环境温度50℃～85℃。通过热力学的方法分析形变过程内能的变化,结果发现,内能随着拉伸不断减小,显示PET纤维在形变过程引发诱导结晶。     

超声激活血卟啉抗肿瘤疗法的研究现状

首先介绍了超声作用的物理机理和血卟啉及其衍生物的化学结构及物理化学性质,对超声激活血卟啉抗肿瘤疗法(声动力学疗法)近15年国内外的试验进展情况进行了总结,对比了不同参数超声系统对不同细胞系肿瘤的作用效果。重点探讨了超声激活血卟啉抑制肿瘤增殖的物理、化学和生物学机理,着重介绍了单线态氧机制和自由基理论,并对今后的基础研究和临床实践进行了展望。     

食管癌的超声诊断及应用进展

食管癌是消化道的恶性肿瘤,早发现、早诊断和早治疗是降低食管癌死亡率的关键因素.目前食管癌的诊疗方法有超声内镜(EUS)、CT、MRI及正电子发射断层现象.但是检测方法各有优势和劣势.EUS能清晰诊断肿瘤浸润深度和淋巴结转移情况,且对食管癌进行分期.另外,EUS可用于放化疗后的评估和辅助疾病的治疗.本研究对食管癌的超声诊...     

高能聚焦超声热治疗恶性肿瘤的初步探索

目的 了解HIFU技术治疗癌瘤的临库效果和安全性。方法 应用FEP-BY01型高能聚焦超声肿瘤治疗机临床治疗78例中晚期腹腔、盆腔、多种脏器癌瘤,并将全部病例分为空腔脏器和实质脏器癌瘤两大类,按各自的标准进行疗效判断,并从疼痛、皮肤的灼伤、腔肠出血、穿孔及其它方面进行安全判断。结果 空腔脏器肿瘤32例,出院时65.6%肿瘤脱落消失,34.4%萎缩。实质脏器癌瘤46例;治疗后15.6%显著疗效,80.4%有效,无效4.3%（因肋骨阻挡）,与放化疗合用可加速肿瘤脱落或萎缩。结论 HIFU技术对控制肿瘤有肯定疗效,并且安全可靠,值得推广应用;其相关医学基础研究须尽快开展。     

A Functional CT Contrast Agent for In Vivo Imaging of Tumor Hypoxia

Hypoxia, which has been well established as a key feature of the tumor microenvironment, significantly influences tumor behavior and treatment response. Therefore, imaging for tumor hypoxia in vivo is warranted. Although some imaging modalities for detecting tumor hypoxia have been developed, such as magnetic resonance imaging, positron emission tomography, and optical imaging, these technologies still have their own specific limitations. As computed tomography (CT) is one of the most useful imaging tools in terms of availability, efficiency, and convenience, the feasibility of using a hypoxia‐sensitive nanoprobe (Au@BSA‐NHA) for CT imaging of tumor hypoxia is investigated, with emphasis on identifying different levels of hypoxia in two xenografts. The nanoprobe is composed of Au nanoparticles and nitroimidazole moiety which can be electively reduced by nitroreductase under hypoxic condition. In vitro, Au@BSA‐NHA attain the higher cellular uptake under hypoxic condition. Attractively, after in vivo administration, Au@BSA‐NHA can not only monitor the tumor hypoxic environment with CT enhancement but also detect the hypoxic status by the degree of enhancement in two xenograft tumors with different hypoxic levels. The results demonstrate that Au@BSA‐NHA may potentially be used as a sensitive CT imaging agent for detecting tumor hypoxia.     

Emerging Nanotechnology and Advanced Materials for Cancer Radiation Therapy

Radiation therapy (RT) including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT) has been widely used for clinical cancer treatment. However, owing to the low radiation absorption of tumors, high doses of ionizing radiations are often needed during RT, leading to severe damages to normal tissues adjacent to tumors. Meanwhile, the RT efficacies are limited by different mechanisms, among which the tumor hypoxia‐associated radiation resistance is a well‐known one, as there exists hypoxia inside most solid tumors while oxygen is essential to enhance radiation‐induced DNA damages. With the development in nanotechnology, there have been great interests in using nanomedicine strategies to enhance radiation responses of tumors. Nanomaterials containing high‐Z elements to absorb radiation rays (e.g. X‐ray) can act as radio‐sensitizers to deposit radiation energy within tumors and promote treatment efficacy. Nanoscale carriers are able to deliver therapeutic radioisotopes into tumors for internal RIT, or chemotherapeutic drugs for synergistically combined chemo‐radiotherapy. As uncovered in recent studies, the tumor microenvironment could be modulated by various nanomedicine approaches to overcome hypoxia‐associated radiation resistance. Herein, the authors will summarize the applications of nanomedicine for RT cancer treatment, and pay particular attention to the latest development of ‘advanced materials' for enhanced cancer RT.     

Development of an In Situ Cancer Vaccine via Combinational Radiation and Bacterial‐Membrane‐Coated Nanoparticles

Neoantigens induced by random mutations and specific to an individual's cancer are the most important tumor antigens recognized by T cells. Among immunologically “cold” tumors, limited recognition of tumor neoantigens results in the absence of a de novo antitumor immune response. These “cold” tumors present a clinical challenge as they are poorly responsive to most immunotherapies, including immune checkpoint inhibitors (ICIs). Radiation therapy (RT) can enhance immune recognition of “cold” tumors, resulting in a more diversified antitumor T‐cell response, yet RT alone rarely results in a systemic antitumor immune response. Therefore, a multifunctional bacterial membrane‐coated nanoparticle (BNP) composed of an immune activating PC7A/CpG polyplex core coated with bacterial membrane and imide groups to enhance antigen retrieval is developed. This BNP can capture cancer neoantigens following RT, enhance their uptake in dendritic cells (DCs), and facilitate their cross presentation to stimulate an antitumor T‐cell response. In mice bearing syngeneic melanoma or neuroblastoma, treatment with BNP+RT results in activation of DCs and effector T cells, marked tumor regression, and tumor‐specific antitumor immune memory. This BNP facilitates in situ immune recognition of a radiated tumor, enabling a novel personalized approach to cancer immunotherapy using off‐the‐shelf therapeutics.     

Erythrocyte‐Membrane‐Enveloped Perfluorocarbon as Nanoscale Artificial Red Blood Cells to Relieve Tumor Hypoxia and Enhance Cancer Radiotherapy

Hypoxia, a common feature within many types of solid tumors, is known to be closely associated with limited efficacy for cancer therapies, including radiotherapy (RT) in which oxygen is essential to promote radiation‐induced cell damage. Here, an artificial nanoscale red‐blood‐cell system is designed by encapsulating perfluorocarbon (PFC), a commonly used artificial blood substitute, within biocompatible poly(d ,l ‐lactide‐co‐glycolide) (PLGA), obtaining PFC@PLGA nanoparticles, which are further coated with a red‐blood‐cell membrane (RBCM). The developed PFC@PLGA‐RBCM nanoparticles with the PFC core show rather efficient loading of oxygen, as well as greatly prolonged blood circulation time owing to the coating of RBCM. With significantly improved extravascular diffusion within the tumor mass, owing to their much smaller nanoscale sizes compared to native RBCs with micrometer sizes, PFC@PLGA‐RBCM nanoparticles are able to effectively deliver oxygen into tumors after intravenous injection, leading to greatly relieved tumor hypoxia and thus remarkably enhanced treatment efficacy during RT. This work thus presents a unique type of nanoscale RBC mimic for efficient oxygen delivery into solid tumors, favorable for cancer treatment by RT, and potentially other types of therapy as well.     

Renal Clearable Theranostic Nanoplatforms for Gastrointestinal Stromal Tumors

Advances in molecular imaging modalities have accelerated the diagnosis and treatment of human diseases. However, tumors less than 1 cm in size still remain difficult to localize by conventional means because of the difficulty in specific targeting/delivery to the tumor site. Furthermore, high nonspecific uptake in the major organs and persistent background retention results in low tumor-to-background ratio. The targeting and therapy of gastrointestinal stromal tumors (GIST) using nonsticky and renal clearable theranostic nanoparticles (a.k.a. H-Dots) are demonstrated. H-Dots not only target GIST for image-guided surgery, but also tailor the fate of anticancer drugs such as imatinib (IM) to the tumor site resulting in efficient treatment of unresectable GIST. In addition, H-Dots can monitor targetability, pharmacokinetics, and drug delivery, while also showing therapeutic efficacy in GIST-bearing xenograft mice following surgical resection. More importantly, IM loaded H-Dots exhibit lower uptake into the immune system, improved tumor selectivity, and increased tumor suppression compared to free IM, which accumulates in the spleen/liver. Precisely designed H-Dots can be used as a promising theranostic nanoplatform that can potentially reduce the side effects of conventional chemotherapies.     

Manganese Dioxide Coated WS2@Fe3O4/sSiO2 Nanocomposites for pH‐Responsive MR Imaging and Oxygen‐Elevated Synergetic Therapy

Recently, the development of multifunctional theranostic nanoplatforms to realize tumor‐specific imaging and enhanced cancer therapy via responding or modulating the tumor microenvironment (TME) has attracted tremendous interests in the field of nanomedicine. Herein, tungsten disulfide (WS₂) nanoflakes with their surface adsorbed with iron oxide nanoparticles (IONPs) via self‐assembly are coated with silica and then subsequently with manganese dioxide (MnO₂), on to which polyethylene glycol (PEG) is attached. The obtained WS₂‐IO/S@MO‐PEG appears to be highly sensitive to pH, enabling tumor pH‐responsive magnetic resonance imaging with IONPs as the pH‐inert T2 contrast probe and MnO₂ as the pH‐sensitive T1 contrast probe. Meanwhile, synergistic combination tumor therapy is realized with such WS₂‐IO/S@MO‐PEG, by utilizing the strong near‐infrared light and X‐ray absorbance of WS₂ for photothermal therapy (PTT) and enhanced cancer radiotherapy (RT), respectively, as well as the ability of MnO₂ to decompose tumor endogenous H₂O₂ and relieve tumor hypoxia to further overcome hypoxia‐associated radiotherapy resistance. The combination of PTT and RT with WS₂‐IO/S@MO‐PEG results in a remarkable synergistic effect to destruct tumors. This work highlights the promise of developing multifunction nanocomposites for TME‐specific imaging and TME modulation, aiming at precision cancer synergistic treatment.     

Albumin‐Templated Manganese Dioxide Nanoparticles for Enhanced Radioisotope Therapy

Although nanoparticle‐based drug delivery systems have been widely explored for tumor‐targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia‐associated resistance to radiation‐induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide ¹³¹I labeled human serum albumin (HSA)‐bound manganese dioxide nanoparticles (¹³¹I‐HSA‐MnO₂) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME). Such ¹³¹I‐HSA‐MnO₂ nanoparticles with suitable sizes during blood circulation show rather efficient tumor passive uptake owing to the enhanced permeability and retention effect, as well as little retention in other normal organs to minimize radiotoxicity. The acidic TME can trigger gradual degradation of MnO₂ and thus decomposition of ¹³¹I‐HSA‐MnO₂ nanoparticles into individual ¹³¹I‐HSA with sub‐10 nm sizes and greatly improves intratumoral diffusion. Furthermore, oxygen produced by MnO₂‐triggered decomposition of tumor endogenous H₂O₂ would be helpful to relieve hypoxia‐associated RIT resistant for those tumors. As the results, the ¹³¹I‐HSA‐MnO₂ nanoparticles appear to be a highly effective RIT agent showing great efficacy in tumor treatment upon systemic administration.     

Synthesis of 2-[18F]Fluoro-L-tyrosine and comparative study of its uptake by rat glioma 35 tumor and by induced inflammation focus in experimental animals

2-[¹⁸F]Fluoro-L-tyrosine (2-[¹⁸F]FTYR), a labeled fluorinated analog of tyrosine, was prepared using chiral phase-transfer catalysis. The radiochemical yield of 2-[¹⁸F]FTYR corrected for radioactive decay was 25±6% (n = 15) at a synthesis time of 110–120 min, including semipreparative HPLC purification. The radiochemical and chemical purity of the product exceeded 99%, and the enantiomeric purity was 98.2±0.7% (n = 15). The uptake of 2-[¹⁸F]FTYR by tumors and abscesses in laboratory animals was studied. The ratios of radioactivity uptake by tumor or imflamed tissue to that of an intact muscle tissue were calculated. Within the time of experiment, the tumor/muscle ratio exceeds the abscess/muscle ratio. The results obtained allow 2-[¹⁸F]FTYR to be considered as potentially useful radiotracer for differential diagnostics of tumors and inflammations by PET.