PSMA PET在前列腺癌复发患者诊断及治疗中的应用

前列腺癌是老年男性中最常见的恶性肿瘤之一,由于我国人民寿命的延长及生活方式西化,其发病率逐年增高.随着根治性前列腺切除术(RP)和根治性放疗(RT)的普及,患者的预后得到了极大的改善,但仍有部分患者出现复发.常规的成像手段很难检测到早期的复发病变.近年来前列腺癌基于前列腺特异性膜抗原(PSMA)的正电子发射断层扫描(P...     

99mTc标记PSMA小分子抑制剂靶向前列腺癌分子影像初步临床研究

背景与目的：前列腺特异性膜抗原(prostate-speciifc membrane antigen,PSMA)在前列腺癌细胞表面特异性高表达,是前列腺癌诊断和治疗的极具有吸引力的靶点。放射性核素标记的PSMA小分子抑制剂能够高效、特异性探测前列腺癌病灶并进行分期。本研究初步探讨99mTc标记PSMA小分子抑制剂(HYNIC-Glu-Urea-A,简称99mTc-PSMA)SPECT/CT显像诊断前列腺原发灶和转移灶的价值。方法：24例前列腺癌和1例前列腺增生患者静脉注射99mTc-PSMA 2 h后行全身平面扫描和腹盆部SPECT/CT断层显像,采用感兴趣区技术计算肿瘤和肌肉摄取99mTc-PSMA比值(T/N)进行半定量分析,评价全身平面显像结合断层显像检测前列腺癌原发灶和(或)转移灶的灵敏度和特异度,分析99mTc-PSMA阳性率与前列腺癌特异性抗原(prostate-speciifc antigen,PSA)水平和Gleason评分的关系。结果：以患者为单位,99mTc-PSMA SPECT/CT对前列腺癌原发灶或转移灶检测的灵敏度为72.7%(16/22)、特异度为100%(3/3)。99mTc-PSMA阳性患者,(中位数17.31 ng/mL,范围2.26~3239.00 ng/mL)水平明显高于99mTc-PSMA阴性患者PSA(中位数0.49 ng/mL,范围0.07~9.28 ng/mL)(Z=-3.51,P<0.001);在初诊和PSA大于2 ng/mL的复发患者中,99mTc-PSMA阳性率明显提高,灵敏度达94.1%(16/17);99mTc-PSMA的阳性率与Gleason评分高低无关(Z=-0.69,P=0.52)。结论：99mTc-PSMA全身平面显像结合局部SPECT/CT断层显像对前列腺癌原发灶和转移灶的探测有较高应用价值,灵敏度及特异度均较高。     

功能化PSMA在前列腺癌核素靶向治疗中的研究进展

前列腺癌（PCa）是男性生殖系统发病率最高的恶性肿瘤。研究证实,前列腺特异性膜抗原（PSMA）是一种有效的前列腺癌诊疗靶点。治疗核素177Lu/90Y标记的抗PSMA小分子/多肽/单抗表现出重要的抑癌活性,但也产生腺体、骨髓的特异性摄取和肾脏的非特异性摄取带来的正常器官损伤。而且小分子/多肽易于经循环系统清除,基于小分子/多肽的放射性靶向治疗往往需要较高剂量或频繁给药,导致在抑制肿瘤的同时,也产生难以预料的器官毒性。放射性核素靶向治疗依赖于将放射性核素传递到肿瘤表达的受体,但配体与受体结合容量有限。为提高核素的使用效率,延长核素治疗型PSMA分子探针的体内代谢,增加靶/非靶比值,对PSMA分子探针进行功能化修饰以期改善药代动力学行为的研究已经取得了巨大进展。本文就近年功能化PSMA分子探针在前列腺癌核素靶向治疗中的临床转化及临床研究展开综述。     

68Ga-DOTA-PDL1P的设计合成及其在黑色素瘤小鼠模型中的应用研究

背景与目的：以程序性死亡[蛋白]-1(programmed death-1,PD-1)/程序性死亡[蛋白]配体-1(programmed death ligand-1,PD-L1)抑制剂为代表的免疫治疗药物在临床上获得巨大成功,但整体有效率差异很大。现阶段在肿瘤开始治疗前,检测患者PD-1/PD-L1的表达情况是临床用药的重要依据,但目前检测PD-L1表达的方法需要获取患者的标本,而获取标本存在创伤性。因此,迫切需要开发一种无创性活体内特异性检测PD-L1表达的方法。我们设计合成了一种新型靶向PD-L1多肽的正电子发射断层显像(positron emission tomography,PET)显像剂⁶⁸Ga-DOTA-PDL1P,本研究通过对⁶⁸GaDOTA-PDL1P的标记率、放射化学纯度及稳定性进行质量控制评估,并在黑色素瘤小鼠模型中进行应用评价,以期获得有转化前景的⁶⁸Ga-DOTA-PDL1P新型免疫PET探针。方法：利用镓-68 (⁶⁸Ga)标记DOTA-PDL1P,并对其放射性化学纯度和...     

靶向前列腺特异性膜抗原药物68Ga-SC691两种前列腺癌小鼠模型micro-PET/CT比较研究

目的 比较分析靶向前列腺特异性膜抗原(PSMA)的新型特异性分子探针在不同放射生物模型中的特性,以寻求评估此类放射性药物的合理生物模型。方法 采用人源性前列腺癌细胞LNCaP、22RV1对靶向PSMA诊断的药物⁶⁸Ga-SC691进行体外细胞摄取内化实验,测定及比较分析2种细胞对⁶⁸Ga-SC691的结合能力。采用SPF级别NOD/SCID鼠建立LNCaP、22RV1荷瘤鼠模型,经尾静脉注射⁶⁸Ga-SC691后进行生物分布和小动物PET/CT成像研究,计算并比较肿瘤、肾脏、血液和各主要脏器的摄取值。结果 体外结合实验显示,LNCaP细胞对⁶⁸Ga-SC691的摄取高于22RV1细胞,在孵育2 h后,(46.01±2.43)%细胞摄取,22RV1细胞摄取为(2.20±0.58)%,t=22.62,P=0.000 1。小鼠体内分布结果表明,标记物主要经肾脏代谢,2种生物模型药代动力学特点类似,但在LNCAP荷瘤鼠肿瘤部位有更高的放射性摄取,在药物注射30 min时,其放射性摄取值在LNCaP模型中为(...     

PET-CT在脑胶质瘤放射治疗及随访中的应用和研究进展

脑胶质瘤是颅内最常见的原发性中枢神经系统肿瘤, 术后放疗是其重要治疗手段。目前CT和MRI在脑胶质瘤放疗靶区设计中被广泛应用, 但对于肿瘤范围、复发、放射性坏死、预后等方面的评估仍然存在一定不足。正电子发射断层显像(PET)-CT将PET的分子影像与CT的解剖结构影像融于一体, 在脑胶质瘤的诊断和鉴别诊断中具有重要价值。随着多模态影像技术在放疗中推广应用, PET-CT分子影像作为重要的补充, 有助于脑胶质瘤靶区的勾画和精准放疗的开展, 有益于脑胶质瘤患者的预后和随访。本文对PET-CT在脑胶质瘤诊断、治疗及随访中的应用和研究进展进行综述。     

PET-CT在脑胶质瘤放射治疗及随访中的应用和研究进展北大核心CSCD

脑胶质瘤是颅内最常见的原发性中枢神经系统肿瘤,术后放疗是其重要治疗手段。目前CT和MRI在脑胶质瘤放疗靶区设计中被广泛应用,但对于肿瘤范围、复发、放射性坏死、预后等方面的评估仍然存在一定不足。正电子发射断层显像(PET)-CT将PET的分子影像与CT的解剖结构影像融于一体,在脑胶质瘤的诊断和鉴别诊断中具有重要价值。随着多模态影像技术在放疗中推广应用,PET-CT分子影像作为重要的补充,有助于脑胶质瘤靶区的勾画和精准放疗的开展,有益于脑胶质瘤患者的预后和随访。本文对PET-CT在脑胶质瘤诊断、治疗及随访中的应用和研究进展进行综述。     

3.0T MR小视野扩散加权成像联合68Ga-PSMA-11 PET-CT对前列腺癌的诊断价值

目的 研究3.0T MR小视野扩散加权成像(rFOV DWI即FOCUS)联合⁶⁸Ga-前列腺特异膜抗原(PSMA)-11 PET/CT对前列腺癌的诊断价值。方法 前瞻性研究90例疑似前列腺癌患者,均行3.0T MR FOCUS与⁶⁸Ga-PSMA-11 PET/CT检查,然后行手术或穿刺活检的病理检查。将两种检查方式分别得到的ADC、SUV_max值作为诊断指标,计算SUV_max/ADC比值,采用受试者工作特征(ROC)曲线分析前列腺癌诊断效能。结果 90例患者经病理检查确诊49例前列腺癌,41例前列腺增生。前列腺增生的ADC值、SUV_max、SUV_max/ADC分别为(1.24±0.28)×10^-3mm²/s、5.86±2.71、5.41±3.80,前列腺癌分别为(0.88±0.23)×10^-3mm²/s、16.63±9.67、22.73±18.21,前列腺癌的ADC...     

^(68)Ga-FAPI-04 PET/CT在胰腺癌与胰腺炎鉴别诊断中的价值北大核心

目的:探讨^(68)Ga-FAPI-04 PET/CT在胰腺癌与胰腺炎鉴别诊断中的应用价值。方法:回顾性分析西南医科大学附属医院核医学科2020年09月至2021年03月61例^(68)Ga-FAPI-04 PET/CT胰腺摄取阳性患者的影像学资料,并根据术后病理、病史、血淀粉酶、血清肿瘤标志物、彩超及MRI检查、随访结果等将病例分为胰腺癌组(16例),急性胰腺炎组(12例),慢性胰腺炎组(11例)及非特异性摄取组(22例),并对这四组病例进行分析。结果:四组间SUV_(max)值比较,差异有统计学意义(P<0.05);Post hoc分别比较,急性胰腺炎组与胰腺癌组的SUV_(max)值均显著大于慢性胰腺炎组及非特异性摄取组;慢性胰腺炎组SUV_(max)值大于非特异性摄取组,差异有统计学意义(P<0.05);当尤登指数为0.773时,SUV_(max)分界值为6.45,此时^(68)Ga-FAPI-04 PET/CT对应的灵敏度为90.9%,特异度为86.4%,准确性为87.9%,阳性预测值76.9%,阴性预测值95.0%;急性胰腺炎组与胰腺癌组的SUV_(max)值差异没有统计学意义,但通过摄取示踪剂的形态及同机CT表现可进行鉴别;胰腺癌肿块大小与SUV_(max)值呈正相关关系。结论:^(68)Ga-FAPI-04作为一种新的示踪剂,通过PET/CT显像在胰腺疾病的诊断上有很大的潜力,在鉴别胰腺病灶良恶性方面有重要价值。     

PET/MRI在高级别脑胶质瘤放射治疗中的应用

脑胶质瘤是最常见的原发性神经系统肿瘤,其中高级别胶质瘤生长迅速,常呈浸润性生长,且治疗后易复发,死亡率和致残率都很高。手术切除仍是高级别胶质瘤的首选治疗方法,术后放射治疗则是其重要的辅助治疗手段之一。目前放射治疗多以MRI图像指导靶区的勾画,但MRI在肿瘤显像方面仍存在局限性。随着多种放射性示踪剂的研究及应用,PET能够通过肿瘤组织的代谢变化来反映肿瘤的浸润范围,还有助于鉴别放射性坏死与肿瘤复发。PET/MRI的联合应用在高级别脑胶质瘤的放射治疗中具有很好的应用前景。     

前列腺特异性膜抗原PET/CT特异性分子显像在非前列腺癌诊断中的应用

前列腺特异性膜抗原（PSMA）是由前列腺上皮细胞分泌的一种Ⅱ型谷氨酸缩肽酶,特异性高表达于前列腺癌及其转移灶的细胞中,在多数实体瘤部位毛细血管内皮细胞中有较高程度的表达。目前,已有超过二十种PSMA靶向的分子探针用于前列腺癌的诊断与治疗。本文综述了PSMA在除前列腺癌以外的多种实体瘤中的表达情况及PSMA-PET/CT特异性探针在非前列腺癌诊断中的临床应用实例,以期拓展以PSMA为靶点的新型PET探针在肿瘤分子诊断中的临床应用。     

Incremental Value of Post Diuretic 68Ga-PSMA-11 PET-CT in Characterization of Indeterminate lLesions in Prostate Cancer

Objective: The aim of current study is to evaluate the role of diuretic assisted 68Ga-PSMA PET-CT, on image quality and clinical interpretation of indeterminate/equivocal lesions in pre-Lasix imaging of Prostate cancer. Materials and Methods: Forty-five patients underwent baseline 68Ga-PSMA-11 scan 45-60 minutes post tracer injection followed by post Lasix study after ±15 minutes. The contrast to noise ratios (CNR), noise and SUVmax were determined for the focal uptakes in both pre and post Lasix images. All continuous variables were expressed as mean ± SD. Images were assessed by two experienced physicians in order to  evaluate lesion detectability and delineations that have an impact on clinical interpretation. Results: Of total 45 patients, 12/45 (27%) showed unremarkable scan along with 33/45 (73%) showing metastases. Sixteen out of 45 (36%) of the metastatic scans showed indeterminate/equivocal lesions. In these cases, post Lasix study showed false negative findings in 7/45 (16%), better delineation of lesions 10/45 (22%), better confidence towards reporting lesions as abnormal in 5/45 (11%) with an overall 11/45 (24%) of the cases who showed increase in the number of the lesions after the Lasix study. The overall CNR was evaluated using Wilcoxon Rank test (p-value = 0.02) which suggested significant improved ratios in the post-Lasix imaging by 49.6%±24.5. There was a substantial agreement (k =0.76) between the physicians when comparing the lesion clarity and delineation in post Lasix images. The average score for physician one and two being 2.4 ±0.71 and 2.53±0.52 respectively. Conclusion: Post diuretic 68Ga-PSMA imaging at ± 15 minutes clears the unwanted activity in the urinary tract which in turn improves the contrast to noise ratios. Thus leading to decline in false positive findings, improved diagnostic certainty of physician and better detection of indeterminate lesions in 68Ga-PSMA imaging.     

Results of a Prospective Phase 2 Pilot Trial of 177Lu–PSMA-617 Therapy for Metastatic Castration-Resistant Prostate Cancer Including Imaging Predictors of Treatment Response and Patterns of Progression

Background

¹⁷⁷Lu–PSMA-617 (Lu-PSMA) is an emerging therapy in men with metastatic castration-resistant prostate cancer. Paired theranostic agents have the potential to visually identify phenotypes that will respond to targeted therapy. This study examined the value of ⁶⁸Ga-HBEDD PSMA-11; prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in Lu-PSMA therapy within the context of a phase 2 prospective pilot trial.

18 F-PSMA-1007 PET/CT在初诊前列腺癌精准评估中的价值及对临床治疗决策的影响

背景与目的： ¹⁸ F-前列腺特异性膜抗原（prostate-specific membrane antigen,PSMA）-1007 PET/CT是目前针对前列腺癌（prostate cancer,PCa）的先进影像学评估方法。探讨 ¹⁸ F-PSMA-1007 PET/CT在初诊PCa中对原发灶和转移灶精准诊断的价值及对临床治疗决策的影响。方法：回顾性分析2018年11月—2019年2月在四川省肿瘤医院确诊并行 ¹⁸ F-PSMA-1007PET/CT检查的18例未治疗PCa患者的临床资料,由核医学医师对PET/CT图像进行盲法阅片分析。采用感兴趣区方法半定量计算肿瘤放射性摄取,以最大标准化摄取值（maximum standardized uptake value,SUV max ）表示。评价 ¹⁸ F-PSMA-1007PET/CT对PCa原发灶和远处转移灶的诊断效能,以及对临床治疗决策的影响,并比较PCa组织放射性摄取与PSA及Gleason评分的相关性。结果： ¹⁸ F-PSMA-1007 PET/CT准确诊断了全部18例PCa,肿瘤组织呈局灶性放射性摄取,灵敏度、阳性预测值和准确率均为100%。发现无转移5例（27.8%）,转移13例（72.2%）,其中10例淋巴结转移（包括4例单纯盆腔淋巴结转移和6例腹膜后等区域外淋巴结转移）,10例骨转移,3例内脏（肺）转移,7例（38.9%）符合高肿瘤负荷PCa。18例PCa患者的前列腺原发灶的中位SUV _max 为13.05,PSA和Gleason评分均与SUV _max 没有显著相关性（P＞0.05）。临床治疗策略方面,除1例患者（合并原发性肺癌）放弃治疗,最终有8例改变了原治疗方案,改变方案率为47.1%（8/17）。结论：¹⁸ F-PSMA-1007 PET/CT对PCa原发灶和转移灶均具有很好的诊断价值和诊断效能,有利于精准分期和对患者制订个体化的治疗方案,并显著影响临床治疗决策。     

前列腺特异性抗原人类激肽释放酶2和前列腺特异的膜抗原在前列腺癌患者外周血表达的临床意义

目的　探讨检测前列腺癌微转移的灵敏和特异性指标。方法　从 5 1例前列腺癌、33例前列腺增生 (BPH)患者及 32名正常人的外周血中分离单个核细胞 ,用巢式RT PCR方法检测其中前列腺上皮细胞前列腺特异性抗原 (PSA)、人类激肽释放酶 2 (hK2 )和前列腺特异的膜抗原 (PSMA)的表达。结果　PSA、hK2和PSMA在前列腺癌患者外周血中检出的阳性率分别为 5 2 .9%、4 3.1%和6 4 .7% ;正常人和BPH患者假阳性率分别为 6 .2 %、7.7%和 4 .6 % ,3项指标差异均有显著性 (P <0 .0 1)。各临床分期 (局限癌、侵袭性癌和转移癌 )间 ,PSA和hK2的阳性检出率差异无显著性 ;PSMA在各期前列腺癌中阳性检出率均较PSA和hK2高 ,且随临床分期进展 ,其阳性检出率亦增加 (P <0 .0 5 )。结论PSMA对前列腺癌诊断、治疗方案的选择及预后评估较PSA和hK2有更大的价值     

68Ga-PSMA PET/CT在前列腺癌复发中的应用进展

 前列腺癌（prostate cancer, PCa）发病率高,根治性治疗后,复发病灶的早期诊断对患者的预后至关重要。前列腺特异性膜抗原（prostate specific membrane antigen,PSMA）是一种在PCa中高表达的跨膜糖蛋白,利用核素⁶⁸Ga标记其小分子抑制剂作为显像剂,进行PET/CT显像,可以得到反映PCa病灶在体内分布的影像。欧美很多国家已经将68Ga-PSMA PET/CT应用于寻找PCa患者复发病灶,并取得了很好的效果,该技术在我国还处于起步阶段。本文综述了多个有关⁶⁸Ga-PSMA PET/CT在前列腺癌复发中的研究进展,旨在提高我们对该项新技术的认识水平。     

Development of Gene Therapy Using Prostate-specific Membrane Antigen Promoter/Enhancer with Cre Recombinase/LoxP System for Prostate Cancer Cells under Androgen Ablation Condition

To enhance the efficacy of suicide gene therapy for prostate cancer under androgen deprivation, we designed a promoter system that consists of the prostate-specific membrane antigen (PSMA) promoter/enhancer (PEPM) and Cre-loxP DNA recombination system. We constructed two kinds of plasmids. One plasmid contains a Cre recombinase (Cre) under the control of PEPM and the other expresses CMV-lox-luciferase/herpes simplex virus thymidine kinase (TK). In PSMA-positive LNCaP cells, the promoter activity of the PEPM-Cre plus CMV-lox-luciferase demonstrated 800-fold greater activity compared with that of the PSMA promoter alone. However, no enhancement of the promoter activity was observed in the PSMA-negative cells. Furthermore, in contrast to prostate specific antigen promoter/enhancer (PP), the promoter activity of PEPM did not decrease when the LNCaP cells were cultured in charcoal-stripped fetal bovine serum (CFBS). In an in vitro gene therapy model with LNCaP cells, the cell growth inhibition in the presence of ganciclovir (GCV) was more evident in the cells transfected with the PEPM-Cre plus CMV-lox-TK than in the cells with the PP-TK, and the difference in efficacy between the two plasmids was more remarkable when the cells were maintained in CFBS medium. The therapeutic effect of PEPM-Cre plus CMV-lox-TK was also observed in xenografted LNCaP cells on nude mice when the plasmids were directly injected into tumors and GCV was administered intraperitoneally. These findings indicate that the combination of the PSMA promoter/enhancer and the Cre-loxP system can enhance the PSMA promoter activity even under androgen ablation conditions and can exert its anti-tumor effect both in vitro and in vivo.     

Use of a New Hypersensitive Assay for the Detection of Prostate Specific Antigen in Prostate Cancer

We have developed a new hypersensitive enzyme immunoassay forprostate specific antigen (PSA) based on the (MARKIT-M PA) assaybut employing a two-hour incubation of the primary monoclonalantibody. The analytical sensitivity has been determined at0.2 ng/ml, calculated as the mean + three standard deviationsof the zero calibrator. Serum PSA was measured at least onemonth after radical prostatectomy (nine patients) or cystoprostatectomy(six patients). Based on the PSA levels of these patients, therecommended PSA cut-off level indicative of residual diseaseafter radical prostatectomy was 0.4 ng/ml. Increasing (>0.4ng/ml) PSA levels preceded recurrence by eight months in a patientwho developed bone metastasis after radical prostatectomy. Intwo patients treated with endocrine therapy, increasing PSAlevels also preceded clinical evidence of progression by betweeneight and nine months. The study suggests that the newly developedsensitive PSA assay allows for the identification of patientswith disease progression and the early commencement of adjuvanttreatment.