靶向表皮生长因子受体分子探针研究进展

许多恶性肿瘤细胞的增殖、转移以及不良的预后已被证实与表皮生长因子受体（EGFR）的过度表达相关。目前,针对这个靶点,美国食品和药物管理局已经批准了多个靶向EGFR药物,如吉非替尼、厄洛替尼,但治疗效率总体偏低。核医学显像能够在分子水平上评价EGFR的表达水平及其突变程度,从而为临床个性化治疗提供有力依据。笔者简述靶向EGFR分子探针及其存在的缺点,以期为进一步研究提供帮助。     

靶向CXCR4 PET/CT分子探针在肿瘤诊疗中的应用进展

趋化因子受体4（CXCR4）在许多肿瘤细胞表面高表达,它可以作为肿瘤干细胞的标志物,其表达与肿瘤的恶性程度及病人的预后直接相关。靶向CXCR4 PET/CT显像在疾病的诊断、CXCR4靶向治疗病例选择、疗效评价等方面具有很大的应用潜力。就靶向CXCR4 PET/CT分子探针及其在肿瘤诊疗中的应用研究进展进行综述,总结分析各种探针的特点及临床转化情况,为CXCR4临床应用转化提供帮助。     

PET、SPECT及MRS在帕金森病诊断中的应用

PET和SPECT可以在体研究帕金森病患者黑质纹状体多巴胺能系统退变的神经化学、血流动力学及代谢改变,脑血流和代谢的激活研究表明,帕金森病患者补偿运动区和背侧额叶前部运动区的激活功能受损。纹状体多巴胺能神经元退变可以通过PET和SPECT进行定量分析,在帕金森病患者中纹状体对18F标记的多巴摄取明显下降,壳核比尾状核下降明显,且与运动异常症状的严重程度及病程呈负相关。PET和SPECT使无创评价多巴胺受体密度的变化成为可能。同时,MRS可以揭示脑内几种含氢含磷化合物的浓度变化。应用这些互相补充的技术可获得关于帕金森病脑功能的信息。     

靶向Tau蛋白PET分子探针的研究进展

Tau蛋白的异常累积是阿尔茨海默病（AD）及非AD类Tau蛋白病的主要病理学特征,并且与神经变性和认知障碍密切相关。近年来,第一代特异性Tau蛋白PET分子探针已经被研发,并进行了临床试验。因第一代PET分子探针中常出现脱靶结合,促进了具有更高结合力和选择性的第二代特异性Tau蛋白PET分子探针的研发。笔者综述了Tau蛋白PET显像作为AD病理学生物标志物的潜力和Tau蛋白分子探针的最新进展。     

乳腺癌分子成像的应用价值

乳腺癌是女性最常见的恶性肿瘤之一,早期诊断及正确评估其侵袭性是影响乳腺癌病人预后的重要因素。多种分子成像技术(包括超声、磁共振成像、放射性核素显像及光学分子成像)对乳腺癌的诊断、临床亚型判断、治疗方式选择及预后评估均有重要价值。其中,超声靶向微泡治疗和光学分子成像指导乳腺癌手术治疗等技术的发展有望成为乳腺癌治疗的新方式。就多种分子成像技术在乳腺癌中的应用价值予以综述。     

靶向表皮生长因子受体免疫PET显像剂研究进展

表皮生长因子受体(EGFR)在癌症的发生、发展、迁移及新生血管形成中发挥着重要作用,在多种恶性肿瘤中存在过表达。靶向EGFR的免疫正电子发射体层成像(PET)结合了单克隆抗体的高靶向性及PET显像的高敏感度,可定量、无创地监测体内EGFR靶点的表达,从而评估肿瘤靶向治疗的效果,有助于肿瘤病人的个体化治疗,并指导抗癌药物的研发。就靶向EGFR免疫PET显像剂的最新研究进展及临床应用进行综述。     

靶向PD-L1的PET/CT分子探针研究进展

程序性死亡受体1（PD-1）/ 程序性死亡配体1（PD-L1）是肿瘤免疫治疗中重要的免疫检查点,PD-L1主要在肿瘤细胞和肿瘤相关髓样细胞中表达。放射性核素标记的靶向PD-L1分子探针可被PET/CT检测,使PD-L1表达在分子层面可视化,是指导免疫治疗的重要手段。靶向PD-L1的PET探针有抗体、多肽、小分子及其他类,目前部分探针应用于临床。笔者对靶向PD-L1的分子探针及临床应用进行综述。     

PET分子探针在阿尔茨海默病早期诊断中的研究进展

阿尔茨海默病(AD)是最常见的痴呆类型,并随着人口老龄化将会变得越来越普遍.在AD 出现临床症状前数十年脑内就可发生病理改变,临床诊断标准不能准确诊检轻度AD及无症状AD.AD的早期诊断越来越受到重视,对发生在AD早期的不可逆性神经损伤前的干预治疗尤为重要.神经影像标志物是最有发展前途的诊断早期AD的方法,PET功能性...     

胃癌PET/CT分子影像探针的研究进展

胃癌是最常见的消化系统恶性肿瘤之一,预后较差,准确地诊断及分期对胃癌临床治疗决策的制定具有重要意义。放射性核素显像如PET/CT或PET/MR可以在分子或细胞水平对肿瘤进行显像,在胃癌的诊断、分期、再分期和疗效评估方面提供重要的信息。由于传统的正电子核素示踪剂18F-FDG在胃癌的应用中存在一些局限性,多种新型分子探针逐渐被开发并应用于胃癌诊断中。笔者就PET/CT分子影像探针在胃癌诊断中的临床应用现状和研究进展进行综述。     

PET、SPECT及MRS在帕金森病诊断中的应用

PET和SPECT可以在体研究帕金森病患者黑质纹状体多巴胺能系统退变的神经化学、血流动力学及代谢改变，脑血流和代谢的激活研究表明，帕金森病患者补偿运动区和背侧额叶前部运动区的激活功能受损。纹状体多巴胺能神经元退变可以通过PET和SPECT进行定量分析，在帕金森病患者中纹状体对^18F标记的多巴摄取明显下降，壳核比尾状核下降明显，且与运动异常症状的严重程度及病程呈负相关。PET和SPECT使无创评价多巴胺受体密度的变化成为可能。同时。MRS可以揭示脑内几种含氢含磷化合物的浓度变化。应用这些互相补充的技术可获得关于帕金森病脑功能的信息。     

PET/SPECT imaging: From carotid vulnerability to brain viability

Background

Current key issues in ischemic stroke are related to carotid plaque vulnerability, brain viability, and timing of intervention. The treatment of ischemic stroke has evolved into urgent active interventions, as ‘time is brain’. Functional imaging such as positron emission tomography (PET)/single photon emission computed tomography (SPECT) could improve selection of patients with a vulnerable plaque and evaluation of brain viability in ischemic stroke.

Objective

To describe the current applications of PET and SPECT as a diagnostic tool in relation to ischemic stroke.

Methods

A literature search using PubMed identified articles. Manual cross-referencing was also performed.

Results

Several papers, all observational studies, identified PET/SPECT to be used as a tool to monitor systemic atheroma modifying treatment and to select high-risk patients for surgery regardless of the degree of luminal stenosis in carotid lesions. Furthermore, PET/SPECT is able to quantify the penumbra region during ischemic stroke and in this way may identify those patients who may benefit from timely intervention.

Discussion

Functional imaging modalities such as PET/SPECT may become important tools for risk-assessment and evaluation of treatment strategies in carotid plaque vulnerability and brain viability. Prospective clinical studies are needed to evaluate the diagnostic accuracy of PET/SPECT.     

The hidden sentinel node and SPECT/CT in breast cancer patients

Purpose  In a minority of breast cancer patients, lymphoscintigraphy shows no lymphatic drainage and ‘hidden’ sentinel nodes may remain undiscovered. The purpose of this study was to explore the additional value of the recently introduced hybrid SPECT/CT in breast cancer patients with axillary non-visualisation on planar images. The role of blue dye and careful palpation of the axilla was evaluated in patients in whom axillary sentinel nodes remained hidden after SPECT/CT. Methods  Fifteen breast cancer patients with non-visualisation on planar lymphoscintigraphy and 13 women with only extra-axillary sentinel nodes underwent SPECT/CT following late planar imaging without re-injection of the radiopharmaceutical. Results  SPECT/CT visualised lymphatic drainage in eight of the 15 patients (53%) with non-visualisation on planar imaging, depicted nine of the 14 harvested sentinel nodes (64%) and three of five tumour-positive sentinel nodes. In two of the 13 patients (15%) with only extra-axillary sentinel nodes on their planar lymphoscintigram, SPECT/CT showed an axillary sentinel node that appeared to be uninvolved. Careful exploration of the axilla with the combined use of blue dye, a gamma probe and intra-operative palpation revealed an axillary sentinel node in the remaining 18 patients. SPECT/CT showed the exact anatomical location of all visualised sentinel nodes. Conclusion  SPECT/CT discovered ‘hidden’ sentinel nodes in the majority of patients with non-visualisation, but was less valuable in patients with only extra-axillary lymphatic drainage on the planar images. Exploration of the axilla in patients with persistent non-visualisation improved the identification of axillary (involved) sentinel nodes.     

New iodinated progestins as potential ligands for progesterone receptor imaging in breast cancer. part 2: in vivo pharmacological characterization

On the basis of the observed high selective binding to both the human and rat progesterone receptor (PR) in vitro, three 17-iodovinyl-substituted nortestosterone derivatives, i.e., the Z-isomer of 17-iodovinyl-19-nortestosterone (Z-IVNT; Z-IPG1) and both the stereoisomers of 17-iodovinyl-18-methyl-11-methylene-19-nortestosterone (E-and Z-IPG2), were selected for radio-iodination and subsequently evaluated as potential radioligands for PR imaging in human breast cancer. Their target tissue uptake, retention, and uptake selectivity were studied in female rats. The distribution studies revealed that PR-mediated uptake in the uterus and ovaries could only be demonstrated for Z-[¹²³I]IPG2. The target tissue uptake selectivity was, however, low, with the highest uterus-to-nontarget tissue uptake ratios observed at 2–4 h postinjection (p.i.), being 4.4, 1.8, and 7.4 for the uterus-to-blood, -fat, and -muscle ratio, respectively. For Z-[¹²³I]IPG2, distribution was also studied in dimethylbenzanthracene (DMBA)-induced mammary tumour-bearing rats and in normal rabbits. Mammary tumour uptake of Z-[¹²³I]IPG2 in the mammary tumour-bearing rat was also found to be PR-specific. In rabbits, higher selective target tissue uptake of Z-[¹²³I]IPG2 was observed than in rats, resulting in uterus-to-blood, -fat, and -muscle ratios of 6.6, 2.2, and 21.3 at 2–4 h p.i., respectively. In conclusion, Z-[¹²³I]IPG2, which displayed high binding affinity for both the human and rat PR in vitro, showed specific PR-mediated target tissue uptake in rats and rabbits in vivo, the uptake selectivity being highest in the latter. Because the binding characteristics appeared to vary between species, a pilot study in breast cancer patients may be needed to decide whether Z-[¹²³I]IPG2 can be of potential use as PR imaging agent in breast cancer.     

The prognostic value of ECG-gated SPECT imaging in patients undergoing stress Tc-99m sestamibi myocardial perfusion imaging

BACKGROUND: The ability of stress radionuclide myocardial perfusion imaging to predict adverse cardiac events is well accepted. As left ventricular systolic function has also been shown to be an important prognostic indicator, the objective of this study was to determine whether electrocardiography (ECG)-gated single photon emission computed tomography (SPECT) functional data add additional power. METHODS AND RESULTS: In this study 3207 patients who underwent stress myocardial perfusion imaging with ECG gating, without early (相似文献   

Near-infrared fluorescence imaging of HER-2 protein over-expression in tumour cells

The aim of this study was to evaluate in vitro and in vivo imaging of HER-2-over-expressing tumours using near-infrared optical imaging. A fluorochrome probe was designed by coupling Cy5.5 to anti-HER-2 antibodies. Cells over-expressing (SK-BR-3 cells) or normally expressing (PE/CA-PJ34 cells) the HER-2 protein were incubated with the probe. After removing unbound probe molecules, fluorescence intensities were determined (a.u.: arbitrary units). Cells were additionally investigated using FACS and laser scanning microscopy. The probe was also injected intravenously into tumours bearing SK-BR-3 (n=3) or PE/CA-PJ34 (n=3). Whole-body fluorescence images were generated and analysed. The incubation of SK-BR-3 cells with the probe led to higher fluorescence intensities [2,133 (±143) a.u.] compared to controls [975 (±95) a.u.]. The results from FACS and immunocytochemical analysis were in agreement with these findings. A distinct dependency between the fluorescence intensity and the cell number used in the incubations was detected. In vivo, the relative fluorescence intensities in SK-BR-3 tumours were higher than in PE/CA-PJ34 tumours at 16–24 h after probe application. HER-2-over-expressing tumours were depictable in their original size. Labelling of HER-2 with Cy5.5 is suitable for in vitro and in vivo detection of HER-2-over-expressing tumour cells.     

Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: Comparison with ECG-gated Tc-99m sestamibi SPECT

BACKGROUND: Although single photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) have evolved considerably over the last decade, there is no recent comparison of diagnostic performance. This study was designed to assess relative image quality, interpretive confidence, and diagnostic accuracy by use of contemporary technology and protocols. METHODS AND RESULTS: By consensus and without clinical information, 4 experienced nuclear cardiologists interpreted 112 SPECT technetium-99m sestamibi and 112 PET rubidium-82 MPI electrocardiography (ECG)-gated rest/pharmacologic stress studies in patient populations matched by gender, body mass index, and presence and extent of coronary disease. The patients were categorized as having a low likelihood for coronary artery disease (27 in each group) or had coronary angiography within 60 days. SPECT scans were acquired on a Cardio-60 system and PET scans on an ECAT ACCEL scanner. Image quality was excellent for 78% and 79% of rest and stress PET scans, respectively, versus 62% and 62% of respective SPECT scans (both p<.05). An equal percent of PET and SPECT gated images were rated excellent in quality. Interpretations were definitely normal or abnormal for 96% of PET scans versus 81% of SPECT scans (p=.001). Diagnostic accuracy was higher for PET for both stenosis severity thresholds of 70% (89% vs 79%, p=.03) and 50% (87% vs 71%, p=.003) and was higher in men and women, in obese and nonobese patients, and for correct identification of multivessel coronary artery disease. CONCLUSION: In a large population of matched pharmacologic stress patients, myocardial perfusion PET was superior to SPECT in image quality, interpretive certainty, and diagnostic accuracy.     

Impact of scan quality on the diagnostic performance of CCTA,SPECT, and PET for diagnosing myocardial ischemia defined by fractional flow reserve

BackgroundScan quality can have a significant effect on the diagnostic performance of non-invasive imaging techniques. However, the extent of its influence has scarcely been investigated in a head-to-head manner.MethodsTwo-hundred and eight patients underwent CCTA, SPECT, and PET prior to invasive fractional flow reserve measurements. Scan quality was classified as either good, moderate, or poor.ResultsDistribution of good, moderate, and poor quality scans was; CCTA; 66%, 22%, 13%; SPECT; 52%, 38%, 9%; PET; 86%, 13%, 1%. Good quality CCTA scans possessed a higher specificity (75% vs. 31%, p = 0.001), positive predictive value (PPV, 71% vs. 51%, p = 0.050), and accuracy (80% vs. 60%, p = 0.009) compared to moderate quality scans, while sensitivity (94%) and negative predictive value (NPV, 88%) were similar to moderate and poor quality scans. Sensitivity (76%), NPV (84%), and accuracy (85%) of good quality SPECT scans was superior to those of moderate (41% p = 0.001, 56% p = 0.010, 70% p = 0.010) and poor quality (30% p = 0.003, 65% p = 0.069, 63% p = 0.038). Specificity (92%) and PPV (87%) of good quality SPECT scans did not differ from scans of diminished quality. Good quality PET scans exhibited high sensitivity (84%), specificity (86%), NPV (88%), PPV (81%) and accuracy (85%), which was comparable to scans of lesser quality. Good quality CCTA, SPECT, and PET scans demonstrated a similar diagnostic accuracy (p = 0.247).ConclusionDiagnostic performance of CCTA, and SPECT is hampered by scan quality, while the diagnostic value of PET is not affected. Good quality CCTA, SPECT, and PET scans possess a high diagnostic accuracy.     

分子影像技术在多药耐药监测中的研究进展

肿瘤的多药耐药（MDR）是导致癌症复发和转移的重要因素。ATP结合盒转运蛋白（ABC转运蛋白）在人体广泛存在,并且ABC转运蛋白的过度表达是导致肿瘤细胞产生MDR的主要原因之一。利用分子影像技术对MDR肿瘤进行早期监测,有利于临床医师制定有效的治疗方案,并在一定程度上能改善肿瘤患者的预后。笔者就分子影像技术在监测MDR方面的研究进展进行简要综述。     

乳腺癌肿瘤浸润性淋巴细胞水平的影像评估进展

肿瘤浸润性淋巴细胞（TIL）是肿瘤免疫中最受关注的生物标志物,TIL对乳腺癌新辅助化疗和免疫治疗有协同作用,可改善临床疗效。目前采用的评估TIL的方法不能全面反映TIL在肿瘤组织中分布的时间和空间异质性,而影像学具有无创、简便和整体性的特点,被预期为评估乳腺癌TIL水平的有效方法。就乳腺MRI、超声以及PET/CT和PET/MRI等影像学方法评估乳腺癌TIL水平的研究进展予以综述。