新型肿瘤特异性核医学分子探针及应用展望

<正>近年来发展非常迅速的分子影像技术已经将肿瘤的影像学诊断提高到肿瘤细胞或组织特异性表达分子的水平,有助于肿瘤的早诊、早治和个体化治疗。从而有效降低肿瘤死亡率。在各种分子影像模态当中,核医学的PET和sPECT最先进入了临床应用。核医学分子探针是核医学分子影像的核心所在。与最常规使用的~(18)FDG相比,文章将主要介绍新型特异性核医学分子探针在肿瘤诊断、疗效评估及个体化治疗方面的应用。     

前言

自1999年美国哈佛大学Weissleder教授提出分子影像概念以来,分子影像技术迅速发展.这一技术可从分子和细胞水平在体观察和评价体内的生物变化过程,具有无创、实时、动态、特异、活体(in vivo)成像等特点,在疾病(特别是肿瘤)的早期诊断、分期、预后评价及治疗方案的选择和疗效评价等方面发挥着重要和不可替代的作用...     

肺癌诊断方法的比较与研究进展

近年来,随着周围环境的恶化,肺癌的发病率最高并且呈现逐年上升的趋势,且其早期表现隐匿,很容易被忽视,很多患者确诊时已属晚期,丧失去了治疗的最佳时机。.本文主要总结和比较了几种传统的肺癌诊断方法如X线片、CT、MRI、PET-CT,并介绍了几种肺癌的最新的诊断技术,比如肺泡灌洗液或血清肿瘤标记物的联合检测、呼出气中的有机化合物的构成分析以及纤维支气管镜镜检技术等。上述方法诊断肺癌的敏感性和特异性各有优势,临床医生在临床工作中应合理应用上述检测方法,必要时联用多种检测手段,尤其要重视支气管肺泡灌洗液癌胚抗原如Cyfra21-1和CEA的联合检测,利用其较高的敏感性以提早发现和诊断肺癌。     

推动精准医疗和伴随诊断产业创新发展

正精准医疗,就是应用现代分子生物学、分子病理学、分子遗传学、分子影像技术、生物信息技术以及目前热门的大数据技术、智能化技术等,结合患者生活环境和临床数据,实现精准的疾病分类和诊断,制定具有个性化的疾病预防和诊疗方案。包括对风险的精确预测,疾病精确诊断,疾病精确分类,药物精确应用,疗效精确评估,疗后精确     

分子影像技术在转化医学中的应用*

摘要：基础医学、药物研发和临床医学是三个不同的的领域,因此这些领域的很多生命科学研究成果经常无法及时应用于临床实 践。转化医学是以疾病为中心,加速将基础研究的成果用于临床诊断和治疗中,旨在有效的将三个领域有机结合在一起。分子影 像学(molecular imaging, MI) 可在活体上、在细胞和分子水平对生物学过程成像并进行定性和定量研究,为转化医学的实现提供 了保证。分子影像技术采用无创的医学影像技术使活体状态下组织细胞中的特殊分子生物学特性得以直观揭示,主要用于对疾 病早期诊断、疾病分期（分层）、疗效监测、指导疾病的个体化治疗以及新药的研发等领域。本文主要介绍分子影像的技术特点、其 在转化医学中发挥的作用以及其在个体化治疗中临床意义进行综述。     

肿瘤化疗药物体外药敏预测实验进展

化学治疗作为全身性常规有效治疗手段之一,在恶性肿瘤治疗过程中占有手术和放射治疗不可替代的地位。有资料显示肿瘤内科治疗及多学科的综合治疗已提高了癌症的疗效。化疗药物抗癌谱往往是根据一般性的常规筛选试验所制定的,但因不同肿瘤类型,甚至同类肿瘤不同个体的化疗疗效差     

肾脏原发性肿瘤CT 成像进展

肾脏原发性肿瘤种类繁多,多为恶性,且各病理亚型的影像表现均有不同。部分良性肿瘤如乏脂性血管平滑肌脂肪瘤、嗜酸细胞瘤难以与其区分,因此术前明确其组织学类型有助于治疗方案制定以及预后评估。CT是检查肾脏肿瘤的重要影像方法之一,除常规平扫、动态增强检查外,CT灌注成像、能量CT及PET-CT等亦提供了诸多信息。本文就其CT成像现状综述如下。     

分子诊断技术在乳腺癌检测中的最新进展

乳腺癌是一种严重危害女性健康的恶性肿瘤,对其致病基因的检测有助于肿瘤早期诊断、精准治疗及预后评估.本文总结了近年来乳腺癌相关的热点基因,并对相关基因的分子诊断技术、检测方法及应用进行了综述.首次评述了数字PCR方法用于乳腺癌分子检测的进展.全面对比不同分子诊断技术的差别与优缺点,为乳腺癌关键基因的检测提供指导建议与理论支持,并对未来发展趋势做出展望.     

分子影像技术在转化医学中的应用

基础医学、药物研发和临床医学是三个不同的的领域,因此这些领域的很多生命科学研究成果经常无法及时应用于临床实践。转化医学是以疾病为中心,加速将基础研究的成果用于,临床诊断和治疗中,旨在有效的将三个领域有机结合在一起。分子影像学（molecularimaging,MI）可在活体上、在细胞和分子水平对生物学过程成像并进行定性和定量研究,为转化医学的实现提供了保证。分子影像技术采用无创的医学影像技术使活体状态下组织细胞中的特殊分子生物学特性得以直观揭示,主要用于对疾病早期诊断、疾病分期（分层）、疗效监测、指导疾病的个体化治疗以及新药的研发等领域。本文主要介绍分子影像的技术特点、其在转化医学中发挥的作用以及其在个体化治疗中临床意义进行综述。     

影像学方法在淋巴瘤疗效评估中的应用

淋巴瘤通过放化疗可获得很高的治愈率。治疗过程中,疗效评估对于评价或调整治疗方案至关重要。基于病灶形态学改变的传统影像学技术如计算机断层扫描(computed tomography,CT)与磁共振成像(magnetic resonance imaging,MRI)技术在评估淋巴瘤疗效时存在一定的局限性;磁共振加权成像(diffusion-weighted imaging,DWI)结合水分子表观弥散系数(apparent diffusion coefficient,ADC)从分子水平反映疾病的病理生理状态,是一种功能成像新技术;而正电子发射断层显像/X线计算机体层成像(Positron emission tomography/computed tomography,PET/CT)将肿瘤的代谢与形态相结合,是一种新型的功能成像技术,已广泛应用于淋巴瘤患者的分期、疗效监测和预后评估中,可较其他影像学技术更准确的评估疗效;PET/MRI技术在淋巴瘤方面的临床应用研究目前尚处于初步阶段,其临床价值尚需进一步探讨。     

Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance

Imaging modalities play an important role in the clinical management of cancer, including screening, diagnosis, treatment planning and therapy monitoring. Owing to increased research efforts during the past two decades, photoacoustic imaging (a non-ionizing, noninvasive technique capable of visualizing optical absorption properties of tissue at reasonable depth, with the spatial resolution of ultrasound) has emerged. Ultrasound-guided photoacoustics is noted for its ability to provide in vivo morphological and functional information about the tumor within the surrounding tissue. With the recent advent of targeted contrast agents, photoacoustics is now also capable of in vivo molecular imaging, thus facilitating further molecular and cellular characterization of cancer. This review examines the role of photoacoustics and photoacoustic-augmented imaging techniques in comprehensive cancer detection, diagnosis and treatment guidance.     

Molecular imaging of proteolytic activity in cancer

The early detection of both primary tumors and metastatic disease continue to be significant challenges in the diagnosis and staging of cancer. The growing recognition of the role of proteinases and proteolytic cascades in both the growth and metastasis of tumors has led to the development not only of therapeutic strategies using proteinase inhibitors, but also of methods to detect and image tumors in vivo via tumor-associated proteolytic activities. These imaging strategies derive from the enhanced sensitivity afforded by amplification that can be obtained by enzymatic processing to increase the efficacy of imaging "contrast agents" coupled with the inherent substrate specificity and selectivity of proteinases. This review describes key proteinases important in cancer progression, the strategies that have been devised to detect and image proteolytic activity in vivo, and the potential for this kind of functional imaging to serve as a marker for targeted therapy. The intent is to draw attention to the developing methods of molecular imaging to facilitate not only cancer diagnosis, but also for devising strategies for individualized targeted therapy and non-invasive monitoring of therapeutic efficacy.     

Clinical value of (18)F-FDG PET-CT in detecting primary tumor for patients with carcinoma of unknown primary

Objective: To investigate the clinical value in detecting occult primary tumors with (18)F-FDG PET-CT whole body imaging. Methods: 120 patients with unknown primary origin were referred for (18)F-FDG PET-CT whole body imaging. All patients were performed (18)F-FDG PET-CT whole body scan. PET-CT images were interpreted by visual inspection and semi-quantitative analysis (standardized uptake value, SUV). Histopathological and formal clinical follow-up findings were used to assess the value of FDG PET-CT. Results: FDG PET-CT was able to detect the primary tumor in 54/120 patients (42.5%). The primary tumors were confirmed by histopathologic and formal clinical follow-up findings, and located in the head and neck (n=17), the lung (n=19), the breast (n=2), the esophagus (n=1), the stomach (n=2), the bile ducts (n=1), the pancreas (n=3), the co1on (n=3), the ovary (n=2), the prostate (n=l), others (n=3). FDG PET results were proved false positive in 9 patients (7.5%), which were located in the head and neck (n=3), the lung (n=1), the gastric (n=1), the colon (n=2), the ovary (n=1), the prostate (n=l). During the clinical follow-up of median 32months (range, 2-45months), primary tumor was found in only 5 patients of 60 cases unidentified by PET-CT (breast cancer, gastric cancer, co1on cancer, prostate cancer and urinary tumors, respectively). The sensitivity, specificity, and accuracy of (18)F-FDG PET-CT in the detection of the primary tumor site were 91.5%, 85.2%, and 88.3%, respectively. Conclusion: (18)F-FDG PET-CT whole body imaging is both a noninvasive and a very sensitive tomographic whole-body imaging modality, allowing for the detection of a primary tumor and complete tumor staging in single examination, which can contribute substantially to selecting appropriate therapeutic methods and evaluating prognosis. Perhaps (18)F-FDG PET-CT whole body imaging should be used as a first-line imaging modality for patients with carcinoma of unknown primary rather than using it after other diagnostic procedures have failed to identify a primary tumor.     

TEP au 18-FDG et cancers ORL : récidive et surveillance post-thérapeutique

Recurrence of head and neck squamous cell carcinomas occurs early and currently, with poor prognosis. Post-therapeutic surveillance aims to diagnose a recurrence as early as possible in order to perform curative salvage therapy. The risk of recurrence is highest in locally advanced cancers. Morphological imaging, including Computed Tomography (CT Scan) and magnetic resonance imaging, can be limited by the anatomic changes following surgery and radiotherapy, and sometimes cannot provide early diagnosis of recurrence. Histology presents some risk of morbidity, especially in irradiated tissues, and sampling error. Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose (FDG) is superior to conventional imaging for the diagnosis and staging of recurrence, especially when it is performed three months after the end of treatments. FDG-PET has high sensitivity and negative predictive value for recurrence, so that further morphological and invasive investigations should not be performed in case of negative examination. On the other hand, because of its limited specificity and positive predictive value, any positive PET finding should be documented, in order to avoid false positives findings. The diagnosis of recurrence is the field of application in which FDP-PET has the greatest impact on head and neck cancer management: it is considered as a standard. However, the interest of FDG-PET during systematic follow-up has not yet been confirmed. PET should only be performed in difficult cases and within evaluation protocols.     

Recommendations of the Spanish Societies of Radiation Oncology (SEOR), Nuclear Medicine & Molecular Imaging (SEMNiM), and Medical Physics (SEFM) on 18F-FDG PET-CT for radiotherapy treatment planning

Positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) is a valuable tool for diagnosing and staging malignant lesions. The fusion of PET and computed tomography (CT) yields images that contain both metabolic and morphological information, which, taken together, have improved the diagnostic precision of PET in oncology. The main imaging modality for planning radiotherapy treatment is CT. However, PET-CT is an emerging modality for use in planning treatments because it allows for more accurate treatment volume definition. The use of PET-CT for treatment planning is highly complex, and protocols and standards for its use are still being developed. It seems probable that PET-CT will eventually replace current CT-based planning methods, but this will require a full understanding of the relevant technical aspects of PET-CT planning. The aim of the present document is to review these technical aspects and to provide recommendations for clinical use of this imaging modality in the radiotherapy planning process.     

Neoadjuvant chemotherapy in head and neck cancer

BACKGROUND: Neoadjuvant chemotherapy has an increasing role in multimodality treatment of advanced head and neck cancer. In this paper we summarize our first results with this treatment. METHOD: Thirty-five, previously untreated, mostly inoperable head and neck cancer patients were given two cycles of Cisplatin and 5FU chemotherapy. We continued the therapy only in case of regression until four cycles, then the patients received surgical and/or radiotherapy according to their status. After the treatment patients' status was regularly evaluated. RESULTS: We detected 4 complete and 20 partial responses after the chemotherapy. Three patients became eligible for a radical operation. At this moment 10 patients are free of tumor, 8 patients died in consequence of the tumor, we have no data in 3 cases, 3 patients are given palliative therapy because of progression, 4 patients are receiving radiotherapy and 7 patients with partial response are candidates for further active oncotherapy. CONCLUSIONS: Although the number of the patients we treated is too small for a statistical analysis, our results are similar to the conclusion of the large randomized studies: after neoadjuvant chemotherapy of advanced head and neck cancer partial response can improve the result of surgical or radiological treatment. Neoadjuvant chemotherapy does not improve survival in advanced head and neck cancer, but it is of great importance because of better quality of life of patients, especially those who had organ preserving therapy.     

The effect of radiotherapy on NKT cells in patients with advanced head and neck cancer

Background

Cancer immunotherapy with NKT cells is a potential new treatment strategy for advanced head and neck cancer. NKT cell therapy is promising due to its unique anti-tumor activity and higher degree of safety compared to current therapies. Radiotherapy is indispensable as a standard treatment for advanced head and neck cancer. To elucidate the possibility of using NKT cells as an adjuvant immunotherapy with radiotherapy, we examined the effect of radiotherapy on NKT cells in patients with head and neck cancer.

Methods

The number, IFN-γ production and proliferation capacity of NKT cells were analyzed before and after 50 Gy radiation therapy in 12 patients with stage IV head and neck squamous cell carcinoma. The cytotoxic activity of NKT cells was examined in vitro.

Results

The number of NKT cells in the blood varied widely between patients. After radiation therapy, the population of CD3 T cells decreased significantly, while the NKT cell population remained stable. The number of NKT cells was the same after radiation therapy as before. IFN-γ production from NKT cells collected just after radiotherapy was impaired after stimulation with exogenous ligand, but the proliferative responses of these NKT cells was enhanced in comparison to those collected before radiation therapy. Furthermore, the proliferated NKT cells displayed a significant level of anti-tumor activity.

Conclusion

NKT cells are relatively resistant to radiation and might therefore be suitable for adjuvant immunotherapy to eradicate remnant cancer cells in patients who have undergone radiation therapy.     

Radiation-induced circulating miRNA expression in blood of head and neck cancer patients

In recent years, scientists have found evidence confirming the aberrant expression of miRNAs in cancer patients compared to healthy individuals. The growing interest in the identification of non-invasive and specific diagnostic and prognostic molecular markers has identified microRNAs as potential candidates in cancer diagnosis, prognosis and treatment response. In the present study, we have analyzed the expression profile of circulating miR-21, -191 and -421 in peripheral blood of head and neck cancer patients (HNC) to investigate a possible modulation of mRNA levels by radiation and to identify the role of mRNA as biomarkers of cancer prognosis. Results showed a modulation of the microRNA expression at different time points after radiotherapy, suggesting that treatment may influence the release of circulating miRNAs depending also on the time interval elapsed since radiotherapy. The expression levels of miR-21, -191 and -421 were higher in blood of patients treated with radiotherapy alone after 6 months from the end of therapy and high levels of them seemed to correlate with the remission of the disease. The trends shown in this study confirmed that miRNAs could be useful prognosis markers and could provide preliminary data for further evaluation in predicting patients’ response to radiotherapy by developing miRNA-based treatments to improve the sensitivity of cancer cells to radiotherapy.     

Omni-wedge technique for increased dose homogeneity in head and neck radiotherapy

Dose homogeneity in head and neck tumour irradiation is a challenging task for conventional radiotherapy due to large anatomic contour irregularities and tissue heterogeneities in irradiation volumes. We present a simple technique based on the omni-wedge concept which uses superimposed fields, orthogonally wedged, to improve target-volumes homogeneity in head and neck tumour irradiation. The routine implementation of this technique is straightforward and easy to achieve with standard radiotherapy equipment and treatment planning software. Our five-year experience in the clinical implementation of this technique is presented.     

影像学在肾癌靶向治疗中的临床应用价值-现状与展望

肾癌为最常见的肾脏恶性肿瘤,其易复发及易出现远隔转移,靶向治疗已逐渐成为肾癌治疗中不可或缺的治疗手段。由于RECIST标准评价实体瘤疗效具有明显的局限性,临床实践中常使用电子计算机断层扫描(CT)、磁共振成像(MRI)评价疗效。随着技术的不断发展,很多新颖的影像学手段如动态增强超声(DCE-US)、正电子发射断层显像(PET-CT)等可以更准确更早期地评价及预测靶向治疗的疗效。本文对肾癌靶向治疗的影像学现状及展望进行综述。