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.     

Synthesis and evaluation of a 125I-labeled iminodihydroquinoline-derived tracer for imaging of voltage-gated sodium channels

In vivo imaging of voltage-gated sodium channels (VGSCs) can potentially provide insights into the activation of neuronal pathways and aid the diagnosis of a number of neurological diseases. The iminodihydroquinoline WIN17317-3 is one of the most potent sodium channel blockers reported to date and binds with high affinity to VGSCs throughout the rat brain. We have synthesized a ¹²⁵I-labeled analogue of WIN17317-3 and evaluated the potential of the tracer for imaging of VGSCs with SPECT. Automated patch clamp studies with CHO cells expressing the Na_v1.2 isoform and displacement studies with [³H]BTX yielded comparable results for the non-radioactive iodinated iminodihydroquinoline and WIN17317-3. However, the ¹²⁵I-labeled tracer was rapidly metabolized in vivo, and suffered from low brain uptake and high accumulation of radioactivity in the intestines. The results suggest that iminodihydroquinolines are poorly suited for tracer development.     

Synthesis and characterization of 123I-CMICE-013: A potential SPECT myocardial perfusion imaging agent

Coronary artery disease (CAD) is a major cause of death in Canada and the United States. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a useful diagnostic test in the management of patients with CAD. The widely used SPECT MPI agents, ^99mTc sestamibi and ^99mTc tetrofosmin, exhibit less than ideal pharmacokinetic properties with decreasing uptake with higher flows. ¹²³I has a similar energy as ^99mTc, an ideal half life, and is readily available from cyclotrons. The objective of this study was to develop an ¹²³I labeled MPI agent based on rotenone, a mitochondrial complex I inhibitor, as an alternative to currently available SPECT MPI agents. Methods: ¹²³I-CMICE-013 was synthesized by radiolabeling rotenone with ¹²³I in trifluoroacetic acid (TFA) with iodogen as the oxidizing agent at 60 °C for 45 min, followed by RP-HPLC purification. The product was formulated in 5% EtOH in 10 mM NaOAc pH 6.5. The inactive analog ¹²⁷I-CMICE-013 was isolated and characterized by NMR and mass spectrometry, and the structure determined. Micro-SPECT imaging studies were carried out in normal and infarcted rats. Biodistribution studies were performed in normal rats at 2 h (n = 6) and 24 h (n = 8) post injection (p.i.). Results: ¹²³I-CMICE-013 was isolated with >95% radiochemical purity and high specific activity (14.8–111 GBq/μmol; 400–3000 mCi/μmol). Structural analysis showed that rotenone was iodinated at 7′-position, with removal of the 6′,7′-double bond, and addition of a hydroxy group at 6′-position. MicroSPECT images in normal rats demonstrated homogeneous and sustained myocardial uptake with minimal interference from lung and liver. Absent myocardial perfusion was clearly identified in rats with permanent left coronary artery ligation and ischemia-reperfusion injury. In vivo biodistribution studies in normal rats at 2 h p.i. showed significant myocardial uptake (2.01 ± 0.48%ID/g) and high heart to liver (2.98 ± 0.93), heart to lung (4.11 ± 1.04) and heart to blood (8.37 ± 3.97) ratios. At 24 h p.i., the majority of ¹²³I-CMICE-013 was cleared from tissues, and a significant amount of tracer was found in the thyroid, indicating in vivo deiodination of the tracer. Conclusion: ¹²³I-CMICE-013 is a promising new radiotracer for SPECT MPI with high myocardial uptake, very good target to background ratios and favorable biodistribution characteristics.     

Intérêt de l’imagerie hybride TEMP/TDM dans la localisation des glandes parathyroïdes ectopiques : à propos de 3 cas

The presence of a parathyroid gland in ectopic position constitutes one of the leading causes of surgery failure. For this purpose, scintigraphy takes a major place in the anatomical localization of pathological parathyroid and so facilitates its treatment. The advent of hybrid cameras combining single photon emission tomography to CT (SPECT/CT) has further strengthened the contribution of this imaging modality in the precise localization of ectopic parathyroid and its anatomical relationships. The objective of our work is to illustrate the interest of hybrid imaging SPECT/CT, compared to planar scintigraphy and ultrasounds within the framework of primary hyperparathyroidism, particularly ectopic situation through three cases.     

Apport de la tomoscintigraphie au technétium 99 m dans le diagnostic des duplications gastriques de l’enfant : à propos d’un cas

Gastric duplications (GD) are rare congenital digestive malformations of the child. Their diagnosis often involves multiple medical imaging modalities ranging from ultrasound to CT or MRI. Scintigraphy is an excellent diagnostic method rarely used especially when the discovery mode of GD is not associated with gastro-intestinal bleeding. We report a case of a non-communicating and non-hemorrhagic GD discovered in a 6-year-old girl whose exploration has benefited many ways including SPECT imaging after intravenous injection of Tc-99 m pertechnetate. Our goal is to focus on the role of scintigraphy in the diagnostic management of the DG of the child and to discuss the opportunity of the other imaging techniques in the exploration of this pathology.     

Apport de la TEMP/TDM pour la détection du ganglion sentinelle dans les cancers du col utérin et de l’endomètre

The sentinel lymph node procedure is still under evaluation for the management of cervical and endometrial carcinomas. The aim of our study was to determine the diagnostic accuracy of single-photon emission computed tomography/computed tomography (SPECT/CT) for preoperative sentinel lymph node mapping in uterine cancers. Sixty-eight patients with cervical (n = 42) or endometrial carcinoma (n = 26) underwent preoperative lymphoscintigraphy for sentinel node mapping. Sentinel node detection rate with conventional planar imaging was similar to that of SPECT/CT (87.1 versus 91.8 %) in the whole cohort. However, SPECT/CT detected a higher number of sentinel nodes in more than one third of patients, affected by either cervical or endometrial carcinoma. The rate of non or insufficiently contributive procedures (lack of uptake or unilateral uptake) in endometrial carcinomas was 47 % with conventional planar imaging, and 30 % with SPECT/CT. Sensitivity of both procedures for the detection of metastatic nodes was 81.8 %, compared to 100 % for the intraoperative combined detection (gamma probe sonde and blue dye). The impact of SPECT/CT for the sentinel lymph node detection in cervical and endometrial carcinomas needs further evaluation. Nevertheless, SPECT/CT may provide additional information when conventional planar imaging detects only unilateral uptake, may improve identification of atypical localizations, and facilitate surgical approach.     

Synthesis and biological evaluation of 9-fluorenone derivatives for SPECT imaging of α7-nicotinic acetylcholine receptor

The α7-nicotinic acetylcholine receptor (α7-nAChR) subtype, is found to have a connection with the pathogenesis of a variety of psychiatric and neurological disorders. Herein, we report the development of radioiodinated 9-fluorenone derivatives as single-photon emission computed tomography (SPECT) imaging tracers for α7-nAChRs. Among the derivatives, the best member of the series 10 (Ki = 2.23 nM) were radiolabeled with ¹²⁵I for in vitro and in vivo studies. The radiotracer [¹²⁵I]10 exhibited robust brain uptake and specifically labeled α7-nAChRs with a peak uptake value of 9.49 ± 0.87%ID/g in brain. Blocking studies demonstrated that the tracer was highly specific toward α7-nAChR. Furthermore, ex vivo autoradiography and micro-SPECT/CT dynamic imaging in mice confirmed the excellent imaging properties. In addition, molecular docking was also performed to rationalize the potency of the chosen compounds towards α7-nAChRs. To conclude, compound 10 could serve as a promising radiotracer for the α7-nAChRs.     

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。