Distribution and dynamics of Tc-99m-pertechnetate uptake in the thyroid and other organs assessed by single-photon emission computed tomography in living mice

Background: Tc-99m pertechnetate is a well-known anion, used for clinical imaging of thyroid function. This gamma emitter is transported by the sodium iodide symporter but is not incorporated into thyroglobulin. Scintigraphy using Tc-99m pertechnetate or 123 iodide represents a powerful tool for the study of sodium iodide symporter activity in different organs of living animal models. However, in many studies that have been performed in mice, the thyroid could not be distinguished from the salivary glands. In this work, we have evaluated the use of a clinically dedicated single-photon emission computed tomography (SPECT) camera for thyroid imaging and assessed what improvements are necessary for the development of this technique. Methods: SPECT of the mouse neck region, with pinhole collimation and geometric calibration, was used for the individual measurement of Tc-99m pertechnetate uptake in the thyroid and the salivary glands. Uptake in the stomach was studied by planar whole-body imaging. Uptake kinetics and biodistribution studies were performed by sequential imaging. Results: This work has shown that thyroid imaging in living mice can be performed with a SPECT camera originally built for clinical use. Our experiments indicate that Tc-99m pertechnetate uptake is faster in the thyroid than in the salivary glands and the stomach. The decrease in Tc-99m pertechnetate uptake after injection of iodide or perchlorate as competitive inhibitors was also studied. The resulting rate decreases were faster in the thyroid than in the salivary glands or the stomach. Conclusions: We have shown that a clinically dedicated SPECT camera can be used for thyroid imaging. In our experiments, SPECT imaging allowed the analysis of Tc-99m pertechnetate accumulation in individual organs and revealed differences in uptake kinetics

From extraction of physiological features with dynamic µ-SPECT imaging to modelling of iodide biodistribution in stomach

This study investigates the potential retention of iodide in the stomach, for a better understanding of the iodide biodistribution in the body and more precisely of its potential antiseptic role. To that end, we will study the uptake of the 99m Tc-pertechnetate (an iodide ana-log) within the murine stomach observed thanks to a SPECT camera. The temporal evolution of the uptake is analysed thanks to a dedicated multi-compartment model. The addressed challenges consist in 1) estimating the time-activity curves for the different compartments, and 2) identifying the model parameters. Real experiments on different subjects demonstrate a quite good coherence of the computed parameters, and the computed parameter values suggested that there is some iodide retention in the stomach wall

Prognostic value of bone marrow tracer uptake pattern in baseline PET scans in hodgkin lymphoma: Results from an international collaborative study

PET/CT-ascertained bone marrow involvement (BMI) constitutes the single most important reason for upstaging by PET/CT in Hodgkin lymphoma (HL). However, BMI assessment in PET/CT can be challenging. This study analyzed the clinicopathologic correlations and prognostic meaning of Different patterns of bone marrow (BM)18F-FDG uptake in HL. Methods: One hundred eighty newly Diagnosed early unfavorable and advanced-stage HL patients, all scanned at baseline and after 2 adriamycin-bleomycinvinblastine-dacarbazine (ABVD) courses with18F-FDG PET, enrolled in 2 international stuDies aimed at assessing the role of interim PET scanning in HL, were retrospectively included. Patients were treated with ABVD 4-6 cycles and involved-field raDiation when needed, and no treatment adaptation on interim PET scanning was allowed. Two masked reviewers independently reported the scans. Results: Thirty-eight patients (21.1%) had focal lesions (fPET1), 10 of them with a single (unifocal) and 28 with multiple (multifocal) BM lesions. Fifty-three patients (29.4%) had pure strong (.liver) Diffuse uptake (dPET1) and 89 (48.4%) showed no or faint (#liver) BM uptake (nPET1). BM biopsy was positive in 6 of 38 patients (15.7%) for fPET1, in 1 of 53 (1.9%) for dPET1, and in 5 of 89 (5.6%) for nPET1. dPET1 was correlated with younger age, higher frequency of bulky Disease, lower hemoglobin levels, higher leukocyte counts, and similar Diffuse uptake in the spleen. Patients with pure dPET1 had a 3-y progression-free survival identical to patients without any18F-FDG uptake (82.9% and 82.2%, respectively, P 5 0.918). However, patients with fPET1 (either unifocal or multifocal) had a 3-y progressionfree survival significantly inferior to patients with dPET1 and nPET1 (66.7% and 82.5%, respectively, P 5 0.03). The k values for interobserver agreement were 0.84 for focal uptake and 0.78 for Diffuse uptake. Conclusion: We confirmed that18F-FDG PET scanning is a reliable tool for BMI assessment in HL, and BM biopsy is no longer needed for routine staging. Moreover, the interobserver agreement for BMI in this study proved excellent and only focal18F-FDG BM uptake should be considered as a harbinger of HL

Normalisation to Blood Activity Is Required for the Accurate Quantification of Na/I Symporter Ectopic Expression by SPECT/CT in Individual Subjects

The utilisation of the Na/I symporter (NIS) and associated radiotracers as a reporter system for imaging gene expression is now reaching the clinical setting in cancer gene therapy applications. However, a formal assessment of the methodology in terms of normalisation of the data still remains to be performed, particularly in the context of the assessment of activities in individual subjects in longitudinal studies. In this context, we administered to mice a recombinant, replication-incompetent adenovirus encoding rat NIS, or a human colorectal carcinoma cell line (HT29) encoding mouse NIS. We used 99mTc pertechnetate as a radiotracer for SPECT/CT imaging to determine the pattern of ectopic NIS expression in longitudinal kinetic studies. Some animals of the cohort were culled and NIS expression was measured by quantitative RT-PCR and immunohistochemistry. The radioactive content of some liver biopsies was also measured ex vivo. Our results show that in longitudinal studies involving datasets taken from individual mice, the presentation of non-normalised data (activity expressed as %ID/g or %ID/cc) leads to ‘noisy’, and sometimes incoherent, results. This variability is due to the fact that the blood pertechnetate concentration can vary up to three-fold from day to day. Normalisation of these data with blood activities corrects for these inconsistencies. We advocate that, blood pertechnetate activity should be determined and used to normalise the activity measured in the organ/region of interest that expresses NIS ectopically. Considering that NIS imaging has already reached the clinical setting in the context of cancer gene therapy, this normalisation may be essential in order to obtain accurate and predictive information in future longitudinal clinical studies in biotherapy

Effect of extracranial lesion severity on outcome of endovascular thrombectomy in patients with anterior circulation tandem occlusion: analysis of the TITAN registry

Introduction Endovascular treatment (EVT) for tandem occlusion (TO) of the anterior circulation is complex but effective. The effect of extracranial internal carotid artery (EICA) lesion severity on the outcomes of EVT is unknown. In this study we investigated the effect of EICA lesion severity on the outcomes of tandem occlusion EVT. Methods A multicenter retrospective TITAN (Thrombectomy In TANdem lesions) study that included 18 international endovascular capable centers was performed. Patients who received EVT for atherosclerotic TO with or without EICA lesion intervention were included. Patients were divided into two groups based on the EICA lesion severity (high-grade stenosis (>= 90% North American Symptomatic Carotid Endarterectomy Trial) vs complete occlusion). Outcome measures included the 90-day clinical outcome (modified Rankin Scale score (mRS)), angiographic reperfusion (modified Thrombolysis In Cerebral Ischemia (mTICI) at the end of the procedure), procedural complications, and intracranial hemorrhage at 24 hours follow-up. Results A total of 305 patients were included in the study, of whom 135 had complete EICA occlusion and 170 had severe EICA stenosis. The EICA occlusion group had shorter mean onset-to-groin time (259 +/- 120 min vs 305 +/- 202 min;p=0.037), more patients with diabetes, and fewer with hyperlipidemia. With respect to the outcome, mTICI 2b-3 reperfusion was lower in the EICA occlusion group (70% vs 81%;p=0.03). The favorable outcome (90-day mRS 0-2), intracerebral hemorrhage and procedural complications were similar in both groups. Conclusion Atherosclerotic occlusion of the EICA in acute tandem strokes was associated with a lower rate of mTICI 2b-3 reperfusion but similar functional and safety outcomes when compared with high-grade EICA stenosis

DOI: 10.1088/0031-9155/58/8/2657 Amplitude-based data selection for optimal retrospective reconstruction in micro-SPECT

Abstract. Respiratory motion can blur the tomographic reconstruction of PET or SPECT images, which subsequently impair quantitative measurements, e.g. in the upper abdomen area. Respiratory signal phase-based gated reconstruction addresses this problem, but deteriorates the signal-to-noise ratio and other intensity-based quality measures. This article proposes a 3D reconstruction method dedicated to micro-SPECT imaging of mice. From a 4D acquisition, the phase images exhibiting motion are identified and the associated list-mode data are discarded, which enables the reconstruction of a 3D image without respiratory artefacts. The proposed method allows a motion-free reconstruction exhibiting both satisfactory count statistics and accuracy of measures. With respect to standard 3D reconstruction (NG3D) without breathing motion correction, an increase of 14.6 % of the mean SUV has been observed, while, with respect to a gated 4D reconstruction (G4D), up to 60 % less noise and an increase of up to 124 % of the SNR have been demonstrated. SPECT, respiratory motion, image-based motion detection, amplitude-based gating and rodent

Evaluation of tetrafunctional block copolymers as synthetic vectors for lung gene transfer

International audienceIn the present study, we evaluated, in mice, the efficacy of the tetrafunctional block copolymer 704 as a nonviral gene delivery vector to the lungs. SPECT/CT molecular imaging of gene expression, biochemical assays, and immunohistochemistry were used. Our dataset shows that the formulation 704 resulted in higher levels of reporter gene expression than the GL67A formulation currently being used in a clinical trial in cystic fibrosis patients. The inflammatory response associated with this gene transfer was lower than that induced by the GL67A formulation, and the 704 formulation was amenable to repeated administrations. The cell types transfected by the 704 formulation were type I and type II pneumocytes, and transgene expression could not be detected in macrophages. These results emphasize the relevance of the 704 formulation as a nonviral gene delivery vector for lung gene therapy. Further studies will be required to validate this vector in larger animals, in which the lungs are more similar to human lungs

Review of the PRIODAC project on thyroid protection from radioactive iodine by repeated iodide intake in individuals aged 12+

International audienceBackground Intake of potassium iodide (KI) reduces the accumulation of radioactive iodine in the thyroid gland in the event of possible contamination by radioactive iodine released from a nuclear facility. The World Health Organization (WHO) has stated the need for research for optimal timing, appropriate dosing regimen, and safety for repetitive iodine thyroid blocking (ITB). The French PRIODAC project, addressed all these issues, involving prolonged or repeated releases of radioactive iodine. Preclinical studies established an effective dose through pharmacokinetic modeling, demonstrating the safety of repetitive KI treatment without toxicity. Summary Recent preclinical studies have determined an optimal effective dose for repetitive administration, associated with pharmacokinetic modeling. The results show the safety and absence of toxicity of repetitive treatment with KI. Good laboratory practice level preclinical studies corresponding to individuals >12 years have shown a safety margin established between animal doses without toxic effect. After approval from the French health authorities, the market authorization of the two tablets of KI, 65 mg/day, was defined with a new dosing scheme of a daily repetitive intake of the treatment up to 7 days unless otherwise instructed by the competent authorities for all categories of population except pregnant women and children under the age of 12 years. Conclusion This new marketed authorization resulting from scientific-based evidence obtained as part of the PRIODAC project may serve as an example to further harmonize the application of KI for repetitive ITB in situations of prolonged radioactive release at the European and international levels, under the umbrella of the WHO .(C2VN), Institut national de recherche pour l'agriculture, l'alimentation et l'environnement (INRAE)

DO MULTIPLE ADMINISTRATIONS OF STABLE IODINE PROTECT POPULATION CHRONICALLY EXPOSED TO RADIOACTIVE IODINE: WHAT IS PRIODAC RESEARCH PROGRAM (2014-22) TEACHING US?

15th Coordination and Planning Meeting of the World-Health-Organization's Radiation-Emergency-Medical-Preparedness-and-Assistance-Network (WHO-REMPAN), Geneva, SWITZERLAND, JUL 03-05, 2017Single dose of potassium iodide (KI) is recommended to prevent the risk of thyroid cancer during nuclear accidents. However in the case of repeated/protracted radioiodine release, a unique dose of KI may not protect efficiently the thyroid against the risk of further developing a radiation-induced cancer. The new WHO guidelines for the use in planning for and responding to radiological and nuclear emergencies identify the need of more data on this subject as one of the four research priorities. The aims of the PRIODAC project are (1) to assess the associated side effects of repeated intakes of KI, (2) to better understand the molecular mechanisms regulating the metabolism of iodine, (3) to revise the regulatory French marketing authorization of 65-mg KI tablets and (4) to develop new recommendations related to the administration of KI toward a better international harmonization. A review of the literature and the preliminary data are presented here