Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Impact of Tumor Burden on Normal Organ Uptake

Purpose

In this study, we aimed to quantitatively investigate the biodistribution of [¹⁸F]DCFPyL in patients with prostate cancer (PCa) and to determine whether uptake in normal organs correlates with an increase in tumor burden.

Procedures

Fifty patients who had been imaged with [¹⁸F]DCFPyL positron emission tomography/computed tomography (PET/CT) were retrospectively included in this study. Forty of 50 (80 %) demonstrated radiotracer uptake on [¹⁸F]DCFPyL PET/CT compatible with sites of PCa. Volumes of interests (VOIs) were set on normal organs (lacrimal glands, parotid glands, submandibular glands, liver, spleen, and kidneys) and on tumor lesions. Mean standardized uptake values corrected to lean body mass (SUL_mean) and mean standardized uptake values corrected to body weight (SUV_mean) for normal organs were assessed. For the entire tumor burden, SUL_mean/max, SUV_mean, tumor volume (TV), and the total activity in the VOI were obtained using tumor segmentation. A Spearman’s rank correlation coefficient was used to investigate correlations between normal organ uptake and tumor burden.

Results

There was no significant correlation between TV with the vast majority of the investigated organs (lacrimal glands, parotid glands, submandibular glands, spleen, and liver). Only the kidney showed significant correlation: With an isocontour threshold at 50 %, left kidney uptake parameters correlated significantly with TV (SUV_mean, ρ?=???0.214 and SUL_mean, ρ?=???0.176, p?<?0.05, respectively).

Conclusions

Only a minimal sink effect with high tumor burden in patients imaged with [¹⁸F]DCFPyL was observed. Other factors, such as a high intra-patient variability of normal organ uptake, may be a much more important consideration for personalized dosimetry with PSMA-targeted therapeutic agents structurally related to [¹⁸F]DCFPyL than the tumor burden.

     

微创经皮肾镜取石术治疗复杂性输尿管上段结石

目的:探讨微创经皮肾穿刺输尿管镜取石术(minPCNL)治疗复杂性输尿管上段结石的优越性及有效性。方法:对接受minPCNL治疗的126例患者资料进行回顾性分析。其中单发输尿管上段结石95例;并患同侧肾结石21例;双侧输尿管上段结石10例。结果:所有患者均行一期穿刺取石,共行142次手术。其中单通道穿刺取石120例,二通道6例。结石清除率95.2%。肾造瘘管平均留置时间5天,平均住院时间8天。2例需要输血,其中1例minPCNL术中输血,1例术后5天并发大出血而改开放手术输血。1例术后3天并发高热,经引流、抗感染治疗1周后治愈。无其他重大并发症。结论:minPCNL治疗复杂性输尿管上段结石安全、可行、疗效确切,与经尿道输尿管镜取石术及传统开放手术相比,解决了重度肾积水输尿管迂曲或结石下方输尿管炎症狭窄导致经尿道输尿管镜无法到达结石的难题,同时亦避免了开放手术创伤大、并发症多的问题。     

肺癌miR-146a表达及其对细胞增殖、侵袭及迁移的影响

目的探讨微小RNA-146a(miR-146a)在肺癌组织和细胞中的表达和甲基化状态,及其对A549细胞增殖、侵袭、迁移的影响及可能机制。方法收集2018年1月至2019年4月在我院行根治性手术的非小细胞肺癌组织和对应癌旁组织,实时荧光定量PCR(QPCR)和甲基化特异性PCR(MSP)检测miR-146a的表达水平和甲基化状态,并分析甲基化状态与肺癌临床病理特征的关系。采用5-氮杂-2’-脱氧胞苷(5-AZA-2’-dC)处理A549细胞(处理组),MTT、Transwell实验和划痕实验检测处理组细胞增殖、侵袭和迁移活性。采用Western blotting检测Notch1和发状分裂相关增强子1(Hes-1)蛋白表达。结果肺癌组织和A549细胞中miR-146a表达量分别为0.63±0.28、0.85±0.11,均低于癌旁正常组织和BEAS-2B细胞(P<0.05)。MSP检测显示肺癌组织miR-146a甲基化率为62.5%(50/80),高于癌旁组织(P<0.05);miR-146a甲基化状态与肿瘤直径、TNM分期、淋巴结转移有关(P<0.05)。处理组细胞miR-146a表达水平为2.15±0.48,高于空白对照组(P<0.05);处理组细胞增殖、侵袭和迁移活性均低于空白对照组(P<0.05)。处理组Notch1蛋白和Hes-1蛋白表达水平分别为0.24±0.05和0.22±0.06,均低于空白对照组(P<0.05)。结论启动子异常甲基化导致在肺癌组织和细胞中miR-146a表达量降低,可能通过减弱对Notch1/Hes-1信号通路的抑制作用,促进肺癌细胞增殖、侵袭和转移,miR-146a有望成为肺癌新的生物治疗靶点。     

同侧和对侧忽略患者SPECT局部脑血流显像的对比研究

目的：探讨同侧和对侧忽略与脑血流改变的部位、范围及程度的关系。方法：对临床确诊为单侧脑卒中、直线平分试验证实有同侧或对侧忽略表现的右利手患者行SPECT脑血流灌注显像，判定局部脑血流量（rCBF)改变部位、范围及程度。结果：同侧忽略可发生在大脑的左、右半球，其最常见损伤部位是额叶，其次中中央沟和顶、枕叶；对侧忽略患者最常见的损伤部位是额叶，其次是颞、顶叶。同侧、对侧忽略患者的病灶rCBF及其降低百分比、病灶范围、数目及缺血体积差异均无显著性。结论：左、右侧脑损伤均可发生同侧忽略，可发生在大脑的各个部位，最常见为额叶，其次为中央沟和顶、枕叶。同侧忽略的病灶rCBF、病灶范围、数目、缺血体积与对侧忽略无明显差异。     

In vitro analysis of cryopreserved alginate–poly‐l‐lysine–alginate‐microencapsulated human hepatocytes

Background: The availability of well‐characterized human hepatocytes that can be frozen and thawed will be critical for cell therapy. We addressed whether human hepatocytes can recover after microencapsulated cryopreservation and investigated whether these cryopreserved microencapsulated hepatocytes can be used for clinical applications. Methods: Adult hepatocytes of 18 separate donors were isolated with a two‐step extracorporeal collagenase perfusion technique. After pre‐incubation at 4 °C for 12–24 h in HepatoZYME‐SFM, hepatocytes were microencapsulated using alginate–poly‐l ‐lysine–alginate microcapsules. The microencapsulated hepatocytes were transferred to a complete medium containing 10% dimethyl sulphoxide. They were immediately placed into an isopropanol progressive freezing container at ?80 °C overnight and immersed in liquid nitrogen the next day. During the post‐thawing culture period, albumin secretion, urea synthesis, cell cycle, mRNA and protein levels, as well as the morphology and pathology structure of pre‐incubation before microencapsulated cryopreservation (PMC) groups were analysed. Results: Compared with the immediate cryopreservation (IC) groups, we found significant improvement in the mRNA and protein levels in the attached cells, and higher secretion of albumin and urea levels after thawing. In the attached cultured human cryopreserved/thawed hepatocytes from the PMC group, albumin production was not significantly different from those of the direct culture groups on days 2, 3 and 4. The preserved morphology in the PMC group compared with the IC group was obvious. Conclusions: The results of the present study suggested recovery of the functional and morphological integrity of human hepatocytes after pre‐incubation at 4 °C for 12–24 h before microencapsulated cryopreservation. These studies offer the possibility for clinical applications in pharmacotoxicology, bioartificial liver and cell therapy in humans.     

半侧空间忽略SPECT rCBF显像研究

目的　探讨半侧空间忽略的发生及程度与脑血流改变的部位、范围及程度间的关系。方法　对临床确诊为单侧脑卒中、忽略组合试验证实有忽略表现的右利手患者行SPECT局部脑血流(rCBF)显像 ,判定rCBF改变的部位、范围及程度。结果　SPECT显像示忽略患者的脑损伤部位最多见于额叶 ,其次是顶叶、枕叶、颞叶、基底节和丘脑。 2个或 2个以上部位的联合损伤更易出现忽略 ,最明显的部位是颞顶枕交界处。病灶区的rCBF及rCBF降低的百分比与忽略程度的相关系数为 - 0 34 (t=- 1.5 ,P >0 .0 5 )和 0 .34 (t=1.47,P >0 .0 5 ) ,病灶的范围、病灶数及病灶缺血体积与忽略程度之间的相关系数分别为 0 .71(t=4.13,P <0 .0 1)、0 .70 (t=4.0 7,P <0 .0 1)和 0 .6 4(t=3.40 ,P <0 .0 1)。结论　忽略患者病灶区的rCBF及rCBF降低的百分比与忽略程度的相关性较小 ,而病灶的范围、病灶数及缺血体积与忽略程度呈正相关。半侧空间忽略可发生于多个大脑部位的损伤 ,多部位联合损伤忽略程度更明显。     

半离体切肝术的实验研究与临床应用

肝脏后方显露困难，使浸及第二肝门处以及包缗肝后段腔静脉的病灶难以得到根治性切除。故设想把肝脏“搬”出体外，切除病灶，再将其“还原”于腹腔内，作者以此为基础首次在临床上实行常温下半离体切肝术。本文着重介绍了动物实验中肝原位，肝离体两种术式的血液动力学和生化的改变，并重点讨论了肝上段腔静脉解剖，半离体切除肝术的操作要点。手术适应症及注意点，该技术的应用，使得一些常规方法不可能切除，肝原位无血切肝术难以     

A Clinical Trial of Optimal Time Interval Between Ablation and Diagnostic Activity When a Pretherapy RAI Scanning Is Performed on Patients With Differentiated Thyroid Carcinoma

This article investigates the association of the time interval between the diagnostic dose and ablation with the stunning effect, when a 74 MBq ¹³¹I pretherapy scanning was performed on patients with differentiated thyroid carcinoma (DTC); the patients who were diagnosed as DTC and would be performed radioiodine (RAI) ablation of thyroid remnants or metastases were recruited during January 2011 and May 2012 in our hospital.Thirty-seven patients with DTC who had the RAI ablation of thyroid remnants or metastases for the first time were recruited. All the patients received a dose of 1850 to 7400 MBq of ¹³¹I for ablation and a diagnostic scan was performed 24 hours after the administration of 74 MBq ¹³¹I before ablation. A posttherapy scan was performed 2 to 7 days after the ablation. The patients were broken down into 3 groups (G1, G2, and G3) according to the interval time between the diagnostic dose and therapy (1–3, 4–7, and >7 days). The fractional concentrations of ¹³¹I in remnants or functional metastases were quantified and expressed as therapeutic/diagnostic (Rx/Dx). The level of significance was set at 0.05.Sixty-seven foci were found both on pretherapy and posttherapy scans, the mean ratio of Rx/Dx was 0.43 ± 0.29, and the ratio of 49 foci (73.13%) was <0.6. The ratios in G1, G2, and G3 were 0.46 ± 0.29, 0.29 ± 0.18, and 0.55 ± 0.33, respectively. The differences between G1 and G2, and G2 and G3 were statistically significant (t = 2.40, P = 0.021 and t = 3.28, P = 0.002), whereas the difference between G1 and G3 was not significant (t = 1.01, P = 0.319).By a diagnostic scan of 74 MBq ¹³¹I, stunning prominently occurs with a time of 4 to 7 days between the diagnostic dose and ablation. We recommend that for less stunning effect, RAI ablation should be performed within 3 days or postponed until 1 week after the diagnostic dose administrated.     

Inconsistent Detection of Sites of Metastatic Non-Clear Cell Renal Cell Carcinoma with PSMA-Targeted [18F]DCFPyL PET/CT

Molecular Imaging and Biology - To investigate the utility of prostate-specific membrane antigen (PSMA)-targeted [18F]DCFPyL positron emission tomography (PET)/X-ray computed tomography (CT)...     

98例血栓闭塞性脉管炎Ⅲ期2～3级的治疗探讨

血栓闭塞性脉管炎(简称脉管炎)是常见的外周血管病之一。根据病情,按全国统一诊断标准分为Ⅰ、Ⅱ、Ⅲ期,并将Ⅲ期患者分为1、2、3级。一般认为Ⅲ期2～3级坏死病例属重症,治疗颇为困难,能否保留患肢,减少高位截肢率是本病的治疗关键,亦是判断疗效的标志之一。自1962年～1979年,我们根据中医辩证施治的法则,研制了临床有效的方药,