Generation of clinical 177Lu SPECT/CT images based on Monte Carlo simulation with GATE

PurposePatient-specific dosimetry in MRT relies on quantitative imaging, pharmacokinetic assessment and absorbed dose calculation. The DosiTest project was initiated to evaluate the uncertainties associated with each step of the clinical dosimetry workflow through a virtual multicentric clinical trial. This work presents the generation of simulated clinical SPECT datasets based on GATE Monte Carlo modelling with its corresponding experimental CT image, which can subsequently be processed by commercial image workstations.MethodsThis study considers a therapy cycle of 6.85 GBq ¹⁷⁷Lu-labelled DOTATATE derived from an IAEA-Coordinated Research Project (E23005) on “Dosimetry in Radiopharmaceutical therapy for personalised patient treatment”. Patient images were acquired on a GE Infinia-Hawkeye 4 gamma camera using a medium energy (ME) collimator. Simulated SPECT projections were generated based on experimental time points and validated against experimental SPECT projections using flattened profiles and gamma index. The simulated projections were then incorporated into the patient SPECT/CT DICOM envelopes for processing and their reconstruction within a commercial image workstation.ResultsGamma index passing rate (2% − 1 pixel criteria) between 95 and 98% and average gamma between 0.28 and 0.35 among different time points revealed high similarity between simulated and experimental images. Image reconstruction of the simulated projections was successful on HERMES and Xeleris workstations, a major step forward for the initiation of a multicentric virtual clinical dosimetry trial based on simulated SPECT/CT images.ConclusionsRealistic ¹⁷⁷Lu patient SPECT projections were generated in GATE. These modelled datasets will be circulated to different clinical departments to perform dosimetry in order to assess the uncertainties in the entire dosimetric chain.     

Illustrations cliniques en pneumologie (embolie pulmonaire)

The examples and clinical cases presented in this section are not intended to be considered as absolute models in terms of image quality or device parameter settings. They must initiate an individual analysis according to CT parameters and image quality. Nevertheless, they present practically different CT levels, which can be used according to the clinical context and the type of device.     

Aurones serve as probes of beta-amyloid plaques in Alzheimer's disease

A novel series of aurone derivatives for in vivo imaging of beta-amyloid plaques in the brain of Alzheimer's disease (AD) were synthesized and characterized. When in vitro binding studies using Abeta(1-42) aggregates were carried out with aurone derivatives, they showed high binding affinities for Abeta(1-42) aggregates at the K(i) values ranging from 1.2 to 6.8 nM. When in vitro plaque labeling was carried out using double transgenic mice brain sections, the aurone derivatives intensely stained beta-amyiloid plaques. Biodistribution studies in normal mice after i.v. injection of the radioiodinated aurones displayed high brain uptake (1.9-4.6% ID/g at 2 min) and rapid clearance from the brain (0.11-0.26% ID/g at 60 min), which is highly desirable for amyloid imaging agents. The results in this study suggest that novel radiolabeled aurones may be useful amyloid imaging agents for detecting beta-amyloid plaques in the brain of AD.     

Validation du logiciel de semi-quantification DaTQUANT® dans l’aide à l’analyse visuelle en TEMP au 123I-FP-CIT dans l’étude des pathologies neurodégénératives

ObjectiveSemi-quantification is a valuable tool increasing the diagnosis accuracy of the single photon emission computer tomography (SPECT) with FP-CIT-¹²³I (DaTSCAN^®), particularly in cases where visual analysis is unclear and especially on the posterior putamen. The DaTQUANT^® software (GE^® Healthcare), allows a quick and simple uptake assessment on several regions of interest. It also provides deviation values compared to a database of healthy subjects obtained in the ENC-DAT project. However, any threshold value is currently validated routinely.Patients and methodsA retrospective study was conducted in 55 patients (33 men, 22 women) referred for a suspicion of neurological disorders and who underwent SPECT imaging with DaTSCAN^® on camera D670 GE^®. Final diagnosis made by neurologist time after the SPECT was established as a reference, reinforced by clinical evolution. Analysis was initially visual without semi-quantitative results, realized by two experimented nuclear physicians, and then semi-quantitative analysis was made by DaTQUANT^® with calculation of Youden indices and ROC curves so as to define threshold values for six regions of interest (caudate, putamen anterior, posterior putamen, bilaterally).ResultsInterobserver match in the blind visual analysis was excellent with kappa coefficient = 0.91, CI at 95% = [0.87–0.95]. The semi-quantitative and statistical analysis by DaTQUANT^® determined pathological threshold values for each region of interest, setting a standard deviation percentage from a database of healthy subjects, worth −16.3% for the right posterior putamen (sensitivity of 100% and specificity of 88%) and −18.3% for the left posterior putamen (sensitivity of 100% and specificity of 97%).ConclusionThe pathological threshold values defined by our study would improve the data analysis obtained from DaTQUANT^® software and would support the DaTSCAN^® visual analysis. Nevertheless, such statistical values are complementary to visual analysis.     

99mTc标记BmK CT及其胶质瘤荷瘤裸鼠的SPECT成像研究

目的:通过放射性核素~(99m)Tc标记BmK CT多肽制备靶向胶质瘤的显像剂,探讨~(99m)?Tc-BmK CT用于胶质瘤显像的可行性。方法:采用BmK CT多肽游离的氨基与DTPA酸酐反应得到BmK CT-DTPA,经99m Tc标记后通过柱层析分离纯化制备~(99m)?Tc-BmK CT。测定标记物在PBS溶液和血清中不同时间点放射性化学纯度,评价BmK CT-~(99m)?Tc体外稳定性。新西兰白兔耳缘静脉注射~(99m)Tc-BmK CT进行SPECT显像,观察不同时间点体内的放射性分布。皮下胶质瘤裸鼠经尾静脉注射~(99m)Tc-BmK CT,观察不同时间点肿瘤的摄取情况;注射后4 h处死裸鼠,分离肿瘤和主要器官进行离体SPECT显像,并用勾画感兴趣区法分析相对放射性计数。结果:~(99m)Tc标记BmK CT多肽标记率大于80%,经柱层析分离纯化后放射性化学纯度大于99%。标记物在PBS和血清稳定性良好,6 h内放射性化学纯度均大于95%,12 h内放射性化学纯度大于90%。正常白兔SPECT显像表明~(99m)Tc-BmK CT主要浓聚在肝脏、脾脏和肾脏,软组织持续显影微弱,甲状腺区及胃肠未见核素浓聚;显像剂主要通过泌尿系统排泄,24 h肾脏与肝脏显影接近。胶质瘤裸鼠SPECT显像表明,注射后4 h肿瘤显像清楚,ROI分析结果显示肿瘤/肌肉比4.26±0.25,标记物在肿瘤内代谢缓慢,8 h肿瘤部位仍有较高摄取。结论:本研究成功制备了~(99m)Tc标记BmK CT多肽,标记物主要被肝、脾和肾摄取,经泌尿系统排泄;~(99m)Tc-BmK CT能够在皮下胶质瘤中浓聚,注射后4 h肿瘤显影清晰,瘤内代谢缓慢,有潜力成为一种新型胶质瘤分子探针。     

Synthesis and biological evaluation of radioiodinated 2,5-diphenyl-1,3,4-oxadiazoles for detecting β-amyloid plaques in the brain

This paper describes the synthesis and biological evaluation of a new series of 2,5-diphenyl-1,3,4-oxadiazole (1,3,4-DPOD) derivatives for detecting β-amyloid plaques in Alzheimer’s brains. The affinity for β-amyloid plaques was assessed by an in vitro binding assay using pre-formed synthetic Aβ42 aggregates. The new series of 1,3,4-DPOD derivatives showed affinity for Aβ42 aggregates with K_i values ranging from 20 to 349 nM. The 1,3,4-DPOD derivatives clearly stained β-amyloid plaques in an animal model of Alzheimer’s disease, reflecting the affinity for Aβ42 aggregates in vitro. Compared to 3,5-diphenyl-1,2,4-oxadiazole (1,2,4-DPOD) derivatives, they displayed good penetration of and fast washout from the brain in biodistribution experiments using normal mice. The novel radioiodinated 1,3,4-DPOD derivatives may be useful probes for detecting β-amyloid plaques in the Alzheimer’s brain.     

Synthesis and evaluation of 99mTc–2-[(3-carboxy-1-oxopropyl)amino]-2-deoxy-d-glucose as a potential tumor imaging agent

The 2-[(3-carboxy-1-oxopropyl)amino]-2-deoxy-d-glucose (CPADG) was synthesized and radiolabeled with ^99mTcO₄⁻ to obtain the ^99mTc–CPADG complex in high yield. It was stable over 6 h in saline at room temperature and in serum at 37 °C. The partition coefficient and electrophoresis results indicated that the complex was hydrophilic and cationic. In vitro cell studies showed there was an increase in the uptake of ^99mTc–CPADG as a function of incubation time and ^99mTc–CPADG was possibly transported via the glucose transporters. The biodistribution of ^99mTc–CPADG in mice bearing S 180 tumor showed that the complex accumulated in the tumor with high uptake and good retention. The tumor/blood and tumor/muscle ratios increased with time and reached 1.91 and 5.05 at 4 h post-injection. Single photon emission computed tomography (SPECT) image studies showed there was an obvious accumulation in tumor sites, suggesting ^99mTc–CPADG would be a promising candidate for tumor imaging.     

Vascular-homing peptides for targeted drug delivery and molecular imaging: Meeting the clinical challenges

The vasculature of each organ expresses distinct molecular signatures critically influenced by the pathological status. The heterogeneous profile of the vascular beds has been successfully unveiled by the in vivo phage display, a high-throughput tool for mapping normal, diseased, and tumor vasculature. Specific challenges of this growing field are targeted therapies against cancer and cardiovascular diseases, as well as novel bioimaging diagnostic tools. Tumor vasculature-homing peptides have been extensively evaluated in several preclinical and clinical studies both as targeted-therapy and diagnosis. To date, results from several Phase I and II trials have been reported and many other trials are currently ongoing or recruiting patients. In this review, advances in the identification of novel peptide ligands and their corresponding receptors on tumor endothelium through the in vivo phage display technology are discussed. Emphasis is given to recent findings in the clinical setting of vascular-homing peptides selected by in vivo phage display for the treatment of advanced malignancies and their altered vascular beds.     

EGFR靶向的PET/SPECT分子成像研究进展

恶性肿瘤的发病率及死亡率逐年递增,分子靶向治疗为癌症治疗带来了新的革命,表皮生长因子受体(EGFR)在癌症发生、发展中发挥重要作用,针对EGFR的分子靶向治疗已成为近年研究热点。目前,已有多种EGFR分子靶向药物应用于临床,但总体有效率偏低。研究表明EGFR过表达和/或突变对治疗效果影响显著,因此治疗前准确评价肿瘤EGFR表达水平及突变状态显得尤为重要。分子成像能够实现活体细胞及分子水平生物学过程成像,并进行定性定量研究,使在体揭示EGFR表达状态成为可能。本文简述EGFR靶向分子成像的研究进展并对不同分子探针成像结果进行比较分析,对不同分子成像探针的功能进行评价,以期有益于EGFR靶向分子成像探针的研发及EGFR靶向分子成像研究。