Sodium Pertechnetate Research Articles

Experience in Validation of Methods for Determination of Radiochemical Impurities in Radiopharmaceuticals

Most important quality attributes of any radiopharmaceutical (RPh) are its radiochemical purity (RCP) or content of radiochemical impurities (RCIs) that have to comply with respective norms and limits. However, at present, there is no unified approach to validation of analytical methods in the context of highly radioactive samples.The aim of the study was to develop an approach to validation of methods for determination of RCI content in RPhs.Materials and methods: the authors determined the content of RCIs in a radiopharmaceutical formulation containing a complex of technetium-99m and methylenediphosphonic acid by the radiometric method after isolation of impurities from the main compound by thin-layer chromatography using silica gel and methyl ethyl ketone (for sodium pertechnetate determination) and silica gel and 13.6% sodium acetate solution (for determination of hydrolysed reduced technetium-99m). The radioactivity was registered by a chromatogram scanner with a detector of gamma-rays with energies from 0.05 to 1.5 MeV.Results: the paper analyses existing official approaches to validation of analytical procedures and compares them with the results of experimental studies described in available publications. It assesses the validation parameters for compliance with the acceptance criteria set forth in the current regulations and substantiates selectivity of chromatographic determination of impurities under the selected test conditions. Coefficients of variation for repeatability, reproducibility, and accuracy did not exceed 4.5, 2.8, and 8.9%, respectively, given the relative error of not more than 10.5%. The study demonstrated signal linearity for the 10-fold dilution of the standardised sodium pertechnetate solution, it also demonstrated correspondence between the applied and detected radioactivity when performing the test in the impurity content range of 0.5–5%. The validation procedure was associated with significant radiation burden for the personnel of the quality control laboratory.Conclusions: the authors suggested a methodological approach to validation of methods for determination of RCI content in technetium-99m-based RPhs. This approach may be used in the development of a guideline on validation of analytical methods for RCP/RCI determination in RPhs, or for introduction of relevant sections into existing documents.

Aerosol regional deposition of electronic cigarette emissions using an original ex vivo respiratory model

AimThere is a need to bridge the data gap concerning the regional deposition of electronic nicotine delivery systems (ENDS) emissions in the airways. The present work aims to experimentally and precisely asses the aerosol regional deposition of ENDS emissions using an ex vivo model of lungs as a complementary approach to a determinist computational model and as an alternative to animal or human in vivo experiments. MethodsThe refill liquid of a recent tank generation ENDS was radiolabelled with sodium pertechnetate. Particle size distributions of the emissions – in mass and in radioactivity – were determined using a cascade impaction technique. The aerosol regional deposition in the airways was both calculated with a determinist computational model and experimentally assessed by gamma-camera imaging on a controlled breathing ex vivo model mimicking intrapleural depression thanks to generation of negative pressures in a sealed enclosure. ResultsThe aerodynamic diameter of the ENDS emissions were 1.03 ± 0.11 μm and 0.87 ± 0.03 μm (mean ± SD) in radioactivity and mass, respectively. The calculations led to a thoracic deposition of 92.89 ± 0.03% and 92.74 ± 0.19% in mass and radioactivity, respectively. The experimental data of thoracic deposition obtained by quantifying the deposited aerosol with planar scintigraphy of the ex vivo model were 91 ± 4%. ConclusionsThe radiolabelling of the refill liquid did not affect the particle size distribution and allowed assessment of the aerosol regional deposition by two-dimensional gamma-camera imaging. When compared, no significant difference of the thoracic deposition between calculation and experimental data could be found. Moreover, data seemed to be in good accordance with previously published data. This work supports the conclusion that this preclinical respiratory model could be used to assess regional deposition of aerosol generated by an ENDS.

Role and limitations of the geometric mean method regarding head rotation in salivary gland scintigraphy: a phantom study.

To investigate the possible influence of head rotation on the results of salivary gland scintigraphy, a phantom study was designed to simulate clinical salivary gland scintigraphy. The quantitative accuracy of regional activity counts was compared for two data acquisition methods involving head rotation: (i) an anterior planar projection-only (ANT) method and (ii) a geometric mean (GM) method using both the anterior and posterior planar projections. The roles and limitations of the GM and ANT methods when used at different head rotation angles were examined. Parallel planar projections of a head phantom with four salivary gland simulators, containing 3.7 MBq 99mTc-sodium pertechnetate, at various rotational settings were acquired using a dual-head gamma camera. The difference between the standard activity counts (no phantom rotation) and the activity counts affected by the phantom rotation was calculated and defined as the rotational bias that decreased the accuracy of activity quantification. For small-angle rotation (≤10°), use of the GM method decreased the bias for all salivary gland simulators. In contrast, the bias of large-angle rotation (>10°) between four salivary gland simulators became conspicuous and complex in both methods. This bias may reflect different attenuation effects caused by displacement of the structures. Our data suggest that the GM method can be used when the head rotation angle is small (≤10°); however, when the head rotation angle is >10°, the non-negligible influence of head rotation should be considered during image acquisition.

Preparation, radiolabeling with 99mTc and 67Ga and biodistribution studies of albumin nanoparticles coated with polymers

ObjectiveTo optimize radiolabeling with 99mTc and 67Ga of albumin nanoparticles coated with 4 differents synthetic polymers and to evaluate their stability in vivo and in vitro, as well as their biodistribution in vivo after intravenous administration. Material and methodsThe nanoparticles were prepared using albumin and NOTA-modified albumin by the desolvation met-hod and coated with 4 different polymers: HPMC, GMN2, GPM2 and GTM2. They were purified, lyophilized and characterized. Radiolabelling with 99mTc was performed with 74MBq of 99mTc sodium pertechnetate, previously reduced with and acid solution of tin chloride at different concentrations (0.003, 0.005, 0.007, 0.01, 0.05 and 0.1mg/ml) and at different times (5, 10, 15, 30 and 60min) and temperatures (room temperature, 40°C and 60°C). Radiolabelling with 67Ga was performed by incubation of the nanoparticles with 37MBq of 67gallium chloride (obtained from commercial gallium-67citrate) at different times (10 and 30min) and temperatures (room temperature, 30°C and 60°C), and posterior purification with microconcentrators. The radiochemical purity was evaluated by TLC. Stability studies of radiolabeled nanoparticles in physiological serum and blood plasma were performed. Biodistribution studies of nanoparticles coated with GPM2 polymer were carried out in Wistar rats after intravenous administration of the nanoparticles. Control animals were carried out with 99mTc sodium pertechnetate and 67Ga chloride. To do so, the animals were killed and activity in organs was measured in a gamma counter. Results99mTc labeling was carried out optimally with a tin concentration of 0.007mg/ml for the GPM2 nanoparticles and 0.005mg/ml for the rest of the formulations, with a radiolabelling time of 10min at room temperature. In the case of 67Ga the label was optimized at 30°C temperature and 30min of incubation. In both cases the radiochemical purity obtained was greater than 97%. The nanoparticles showed high stability in vitro after 48h of labeling (70% nanoparticles labeled with 99mTc and 90% those labeled with 67Ga). Biodistribution studies of nanoparticles 99mTc-GPM2 and 67Ga-NOTA-GPM2 showed a high accumulation of activity in the liver at 2 and 24h after intravenous administration. ConclusionThe labeling procedure with 99mTc and 67Ga of albumin and albumin modified with NOTA nanoparticles allows obtaining nanoparticles with high labeling yields and adequate in vitro stability, allowing their use for in vivo studies.

Fixed 30 mCi 131I-iodine therapy without recombinant human thyroid-stimulating hormone stimulation as an attractive therapeutic alternative in nontoxic nodular goiter.

To analyze outcomes of patients with compressive nontoxic multinodular goiter after 131I-iodine 30 mCi treatment without previous use of recombinant human thyroid-stimulating hormone or methimazole. We evaluated fixed-dose radioiodine therapy outcomes in patients with nontoxic multinodular goiter who did not accept thyroidectomy as a therapeutic option. Laboratory thyroid function and thyroid volume estimated by ultrasound were assessed before and one year after radioiodine therapy. Twenty euthyroid female patients received 30 mCi of 131I-iodine without recombinant human thyroid-stimulating hormone or methimazole pretreatment. Median thyroid volume and Tc-99m sodium pertechnetate thyroid uptake before radioiodine therapy were 68.05 cm (31.3-295.3) and 0.5% (0.1%-1.2%), respectively. One year after radioiodine therapy, thyroid volume decreased to 55.4 cm (19.8-149.9), and merely 4 patients (20%) developed hypothyroidism. Thyroid volume decreased significantly after radioiodine therapy, presenting a variation of -21.1 cm (-161.3 to -0.8) and -30.61% (-73.88 to -1.02), both with P < 0.0001. Thyroid volume variation was positively correlated with thyroid uptake in Spearman's correlation (r = 0.4730; P = 0.0352). The group satisfied with radioiodine therapy (85%, n = 17) showed a significant reduction in thyroid volume, -25.8 cm (-161.3 to -6.2) and -36.74% (-73.88 to -9.95). The dissatisfied group (15%, n = 3) showed -1.0 cm (-2.0 to -0.8) and -1.67% (-3.38 to -1.02) in thyroid volume, P = 0.0081. Patients that complained about dysphagia presented a lower percentage of thyroid volume decrease after radioiodine therapy, -21.97% (-70.12 to -1.02, P = 0.0430). A substantial reduction in thyroid volume associated with a low incidence of hypothyroidism and a high satisfaction rate support the use of conventional radioiodine therapy with a fixed dose of 30 mCi. This therapy is an attractive and cheaper therapeutic alternative in selected patients with nontoxic multinodular goiter.

Validation of a cost-effective alternative for a radiochromatography method to be used in a developing country

IntroductionThe radiochemical purity (RCP) of technetium-99m labelled radiopharmaceuticals (RP) is important to ensure optimal scintigraphic image quality. In low-income settings, it may not be possible to use compendial analytical methods or expensive equipment for radiochemical purity analysis. All radiochemical analysis methods should however be validated against compendial or otherwise proven methods. To ensure the efficacy of RP prepared at Yaoundé General Hospital (YGH) Cameroon, this study cross-validated a cost-effective routine chromatographic method using a simple survey meter technique. A GMP-compliant method used at the University Medical Center Groningen (UMCG), the Netherlands was used as the comparator.MethodsSestamibi, HMDP and DMSA kits currently used at YGH were reconstituted at UMCG with about 2000 MBq of freshly eluted sodium pertechnetate as described by the manufacturer, and spiked with eluate of the same generator to obtain a range of impurity concentrations. Samples of technetium-99m RP were spotted on 1 × 10 cm iTLC-SG strips and developed in appropriate mobile phases. Each strip was first scanned on the chromatogram-scanner used at the UMCG (standard method), and immediately thereafter the strip was cut in two pieces and radioactivity from each portion was counted with a small survey meter from YGH. The percentage RCP for each TLC strip was calculated using both counting methods. Internationally recommended validation parameters and acceptance criteria were used. Student’s paired t-test or ANOVA were used with ‘no significant difference’ designated at a 95% confidence-interval (P ≥ 0.05). Linearity of the survey meter was determined for Tc-99m. Readings obtained with the survey meter were also plotted against the scanner results.Results and discussionThe proposed method proved to be accurate (CV of mean RCP < 2), precise (RSD < 2%), linear (slope close to 1, r2 ≥ 0.99) within the RCP range of approximately 80% to 100%, and robust (P > 0.05). LOD and LOQ were determined for the survey meter. Specificity depends on chemical separation. As we were validating the suitability of a method to quantify radioactivity, specificity was not included in the validation parameters.ConclusionThe proposed method compared well with the standard method and is suitable as a reliable low cost method for limited resource settings.

Preparación, radiomarcaje con 99mTc y 67Ga y estudios de biodistribución de nanopartículas de albúmina con recubrimientos poliméricos

ObjectiveTo optimize radiolabeling with 99mTc and 67Ga of albumin nanoparticles coated with 4 differents synthetic polymers and to evaluate their stability in vivo and in vitro, as well as their biodistribution in vivo after intravenous administration. Material and methodsThe nanoparticles were prepared using albumin and NOTA-modified albumin by the desolvation method and coated with 4 different polymers; HPMC, GMN2, GPM2 and GTM2. They were purified, lyophilized and characterized. Radiolabelling with 99mTc was perfomed with 74 MBq of 99mTc sodium pertechnetate, previously reduced with and acid solution of tin chloride at different concentrations (0.003, 0.005, 0.007, 0.01, 0.05 and 0.1mg/ml) and at different times (5, 10, 15, 30 and 60minutes) and temperatures (room temperature, 40°C and 60°C). Radiolabelling with 67Ga was perfomed by incubation of the nanoparticles with 37 MBq of 67Gallium chloride (obtained from commercial gallium-67 citrate) at different times (10 and 30minutes) and temperatures (room temperature, 30°C and 60°C), and posterior purification with microconcentrators. The radiochemical purity was evaluated by TLC. Stability studies of radiolabeled nanoparticles in physiological serum and blood plasma were perfomed. Biodistribution studies of nanoparticles coated with GPM2 polymer were carried out in Wistar rats after intravenous administration of the nanoparticles. Control animals were carried out with 99mTc sodium pertechnetate and 67Ga chloride. To do so, the animals were killed and activity in organs was measured in a gamma counter. Results99mTc labeling was carried out optimally with a tin concentration of 0.007mg/ ml for the GPM2 nanoparticles and 0.005mg / ml for the rest of the formulations, with a radiolabelling time of 10minutes at room temperature. In the case of 67Ga the label was optimized at 30° C temperature and 30minutes of incubation. In both cases the radiochemical purity obtained was greater than 97%. The nanoparticles showed high stability in vitro after 48hours of labeling (70% nanoparticles labeled with 99mTc and 90% those labeled with 67Ga). Biodistribution studies of nanoparticles 99mTc -GPM2 and 67Ga -NOTA-GPM2 showed a high accumulation of activity in the liver at 2 and 24hours after intravenous administration. ConclusionThe labeling procedure with 99mTc and 67Ga of albumin and albumin modified with NOTA nanoparticles allows obtaining nanoparticles with high labeling yields and adequate in vitro stability, allowing their use for in vivo studies.

Biological Effects of Paullinia cupana (Guarana) in Combination with Whole-Body Vibration Exercise in Wistar Rats

In addition to its nutritional value, Paullinia cupana (guarana) is commonly used in traditional medicine, known for its stimulant and medicinal properties. This investigation evaluated the effects of a guarana extract in combination with whole-body vibration (WBV) exercises on Wistar rats. Rats (male, n = 20) were divided into the following four groups: control (CON), treated with guarana (GUA), submitted to 50 Hz of WBV (WBV-E), treated with guarana and submitted to 50 Hz of WBV (GUA + WBV-E), daily for 6-weeks. Guarana altered (p &lt; 0.05) the uptake of the radiopharmaceutical sodium pertechnetate (Na99mTcO4) in muscle. Additionally, it modified the stool consistency, and in combination with WBV decreased the food intake without modifying body mass. The levels of calcium increased in the groups submitted to WBV exercises (WBV-E and GUA + WBV-E) as compared with the GUA group. The outcomes provide additional evidence of the biological effects of guarana separately or in combination with WBV and supports the use of guarana as a functional food.

Arrêt de production du chrome-51 (51Cr) a usage clinique : quelles alternatives possibles pour les services de radiopharmacie et de médecine nucléaire ?

Last October, the nuclear medicine departments were informed of the closure of the chromium-51 production line for clinical use. This radionuclide has different diagnostic indications in nephrology and hematology. It was therefore essential to set up alternative exploration protocols to overcome this production stoppage. Chromium-51 EDTA has been replaced by technetium-99m DTPA for the determination of glomerular filtration rates. Sodium chromate was substituted by sodium pertechnetate for the determination of globular volumes. A retrospective analysis of the chromium-51 data was performed followed by a prospective study, from January to December 2019 for technetium tracers. One hundred and forty-four patients were included in the study. Forty-two EDTA-51Cr and 30 DTPA-99mTc exams were conducted and compared. There were no significant differences between the methods used to assess renal function (P=0.355). For the determination of blood cell and plasma volumes, 47 tests with 51Cr and 125I and 25 tests with 99mTc and 125I were performed and compared. There were no significant differences in the determination of total (P=0.325) and globular (P=0.148) volumes. The study carried out shows that there is no significant difference between the results obtained with chromium-51 and technetium tracers. As a result, clinical activity was maintained in good conditions.

Treatment of juvenile thyrotoxicosis: A review with emphasis on radioiodine treatment

Objective: The aim of the present study was to evaluate the utility of radioiodine treatment for thyrotoxicosis in childhood and adolescence and to evaluate its outcomes. Methods: This was a retrospective monocentric study of 15 patients (ages 7- 18 years) with a diagnosis of thyrotoxicosis who received iodine-131 (I-131) treatment from January 2015 to July 2019 in the Nuclear Medicine department of King Fahd Medical city. Age, gender, duration of antithyroid drug (ATD) treatment, thyroid uptake, total dose and number of treatments with I-131, and thyroid status at 6 months after treatment were recorded. Results: The outcomes of 15 patients (100% female) treated with radioactive iodine were analyzed to assess the effectiveness of therapy by iodine 131. All children and adolescents underwent 99m technetium thyroid scan with uptake before the procedure. There was no pre-existing ophthalmopathy. Thyroid uptake value was calculated using Sodium Pertechnetate. The average of the treatment activity of iodine 131was 340.4 MBq (247.9-555). There was no vomiting in all cases. Six 6 months after treatment, 7/15 were euthyroid, and 8/15 were hypothyroid. There was no hyperthyroid. All the patients received single radioiodine treatment. Conclusions: Radioiodine treatment is safe and effective for thyrotoxicosis in childhood and adolescence. The results of this present study support the use of radio dine 131 in treating hyperthyroidism in this particular population. It is suitable as a good Second-line therapy for patients who fail to respond to ATD treatment. Although special treatment precautions may be required in this age group, the ease of administration, effectiveness and safety of radio dine 131 continue to make it more and more attractive for initial treatmentof hyperthyroidism, especially when the appropriate treatment activity is prescribed.

The protective effect of iodide intake adjustment and 1,25(OH)2D3 supplementation in rat offspring following excess iodide intake.

Background:In this study, we aimed to investigate the effect of iodide intake adjustment, 1,25(OH)2D3 supplementation, or both, on the thyroid gland of rat offspring.Methods:The offspring of female rats administered 100 times the normal dose of iodide (100 HI; 750 μg/d) during pregnancy and lactation were divided into four different treatment groups. They were either having their iodide intake adjusted from 100 HI to normal iodide intake (7.5 μg/day) or supplemented with 25-hydroxy vitamin D3 [1,25(OH)2D3; 5 μg·kg−1·day−1], or both, for 4 weeks. Thyroid sodium pertechnetate (Na99mTcO4) uptake percentages were measured using single-photon emission computed tomography, while serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and vitamin D3 (VD3) were monitored using enzyme-linked immunosorbent assay. The messenger ribonucleic acid expression of interleukin (IL)-17A, interferon gamma (IFN-γ), and IL-10 in the thyroid gland was measured using quantitative real-time polymerase chain reaction, while the protein expression of thyroid-hormone-receptor α1 (TRα1) and thyroid-hormone-receptor β1 (TRβ1) in the thyroid gland was detected using Western blotting. Haematoxylin and eosin (H & E) and immunofluorescence staining were also used to assess thyroid follicular structure and lymphocytic infiltration in the thyroid glands.Results:The immunofluorescence staining showed CD4+ co-localized with TRβ1 or the vitamin D receptor in thyroid gland cells of rats that were continuously treated with 100 HI. Following iodide adjustment, 1,25(OH)2D3 supplementation, or both, an increase in serum levels of FT3, free thyroxine, and VD3, protein expression of TRα1 and TRβ1 in the thyroid gland cells, and Na99mTcO4 thyroid uptake percentages was observed. The mRNA expression levels of IL-17A and IFN-γ, decreased, while the mRNA expression levels of IL-10 increased in the thyroid cells of each treatment group, except the group with continuous 100 HI intake.Conclusion:Iodide adjustment, 1,25(OH)2D3 supplementation, or both may increase the serum levels of FT3, FT4, and VD3, as well as the protein expression levels of TRα1 and TRβ1, in thyroid cells. In addition, iodide adjustment, 1,25(OH)2D3 supplementation, or both, may potentially reverse the imbalance in pro-inflammatory and anti-inflammatory cytokines (IL-17A, IFN-γ, and IL-10) caused by 100 HI, which may be beneficial in improving Na99mTcO4 thyroid uptake percentages.

Diagnostic model for intelligent recognition of thyroid function by thyroid imaging based on deep neural network

Objective To develop a diagnostic model based on deep neural network for intelligent discrimination of thyroid function. Methods A total of 1 616 patients (283 males, 1 333 females, average age: 52 years) who underwent thyroid imaging between May 2016 and June 2018 were selected. According to the clinical diagnosis, the 1 616 cases included 299 normal thyroid cases, 876 hyperthyroidism cases and 441 hypothyroidism cases. Feature extraction and learning training were performed on 1 000 training set samples by two deep neural network models (AlexNet; deep convolution generative adversarial networks (DCGAN)) using deep learning algorithm. Performance verifications were implemented on 616 test set samples. The consistency between the verification results of the two models and the clinical diagnosis was analyzed by Kappa test. Meanwhile, the time advantage of the intelligent diagnosis models was analyzed. Results The average diagnostic time of AlexNet model was 1 s/case, and the classification accuracy for normal thyroid, hyperthyroidism, hypothyroidism were 82.29%(79/96), 94.62%(369/390), 100%(130/130), respectively. The Kappa value between results of AlexNet model and clinical diagnosis was 0.886 (P<0.05). The average diagnostic time of DCGAN model was 1 s/case, and the classification accuracy for normal thyroid, hyperthyroidism, hypothyroidism were 85.42%(82/96), 95.64%(373/390), 99.23%(129/130), respectively. The Kappa value between results of DCGAN model and clinical diagnosis was 0.904 (P<0.05). Conclusion The deep neural network intelligent diagnosis model can quickly determine the functional status of thyroid gland in thyroid imaging, and it has a high recognition accuracy, thus providing a new method for thyroid image review. Key words: Hyperthyroidism; Hypothyroidism; Diagnosis; Neural networks(computer); Radionuclide imaging; Sodium pertechnetate Tc 99m

Radiopharmaceuticals for diagnosis in nuclear medicine: a short review

Radiopharmaceuticals are radioactive compounds which have a bound radionuclide in their structure, whose purpose is directing the radionuclide to a location to be treated or to obtain images. Nuclear medicine is the medical specialty that employs radiopharmaceuticals, which has presented itself as a tremendously useful ally for medicine assisting in various diagnoses and treatments, especially for cancer. The general objective of this work is to identify the main radionuclides and metal complexes currently used as radiopharmaceuticals. The main metal complexes used as radiopharmaceuticals are compounds of technetium (99mTc) like sodium pertechnetate and methylenediphosphonate MDP-99mTc and other compounds of indium (111In), thallium (201Tl), gallium (67Ga, 68Ga), iodine (123I and 131I), chromium (51Cr), sulphur (35S), phosphorus (32P), fluorine (as fluorodeoxyglucose, 18F-FDG and sodium fluorine, Na18F), which are widely used in the nuclear medicine for diagnosis by imaging. They have been of great importance for the early diagnosis of numerous diseases, mainly cancer.Currently, technetium compounds are the majority of radiopharmaceuticals used in all countries. In Brazil, Institute of Energy and Nuclear Research (IPEN) is one of the most important distributors of radiopharmaceuticals, producing, importing and distributing them to clinics and hospitals over the country.

Effect of excessive iodine intake on the 99Tcm-pertechnetate uptake function of thyroid and the related mechanism

Objective To study the influence of excessive iodine intake on the 99Tcm-pertechnetate uptake function of thyroid and explore the related mechanism. Methods A total of 150 male Wistar rats were divided into normal iodine group (NI group) and 4 high iodine (HI) groups (10HI, 50HI, 100HI and 500HI group) with completely random method. Each group included 30 rats. Rats in HI groups were intragastrically administrated with different concentrations of KIO3, and rats in NI group were administrated with the same amount of distilled water. After a 7 d HI diet, each group was randomly divided into 3 subgroups: 7 d group (HI diet for 7 d), 10 d group (HI diet for 7 d + limiting iodine for 3 d) and 14 d group (HI diet for 7 d + limiting iodine for 7 d). All rats were given 1.85 MBq 99TcmO4-, then the thyroid glands were isolated and weighed 20 min post-injection. The radioactive counts were measured and the thyroid uptake percentage activity of injected dose per gram of tissue (%ID/g) of 99TcmO4- for each sample was calculated. Sodium-iodide symporter (NIS) expression level was analyzed by Western blot. One-way analysis of variance or Welch test was used to compare the differences among groups, and Spearman rank correlation analysis was also used. Results At the same observation time, the %ID/g of 99TcmO4- and NIS expression among different HI groups were statistically significant (F values: 48.825-119.219, all P 0.05). Significant differences of %ID/g of 99TcmO4- and NIS expression were found among different time subgroups in 50HI, 100HI and 500HI groups (F values: 10.442-90.408, all P<0.01). Spearman correlation analysis showed that the concentration of iodine correlated negatively with %ID/g of 99TcmO4- and NIS expression (rs values: -0.853 and -0.950, both P<0.01), while the %ID/g of 99TcmO4- and NIS expression was positively correlated (rs=0.925, P<0.01). Conclusions Excessive iodine intake can inhibit thyroid uptake of 99TcmO4- in rats, which is associated with the down-regulation of NIS expression. The degree of inhibition correlates positively with iodine concentration, and correlates negatively with NIS expression. The degree of recovery of NIS and %ID/g of 99TcmO4- may relate to the time of limiting the iodine intake. Key words: Thyroid gland; Sodium pertechnetate Tc 99m; Iodine; Rats; Sodium/iodide symporter

Evaluation of the tear clearance rate by dacryoscintigraphy in patients with obstructive meibomian gland dysfunction

PurposeTo measure tear clearance values in patients with meibomian gland dysfunction (MGD) with a dynamic nuclear medicine method, namely, dacryoscintigraphy (DSCI). MethodsTwenty-four MGD patients and 24 healthy volunteers were examined. During DSCI one drop of a solution with 100 MBq/mL99mTc sodium pertechnetate was instilled with a micropipette into the lacrimal lake of both eyes. Measurements were performed according to a dynamic data acquisition protocol, which resulted in summed DSCI images. Data were also evaluated separately in special regions of interest (ROI), and consecutive time activity curves were created. Tear clearance (T½) values were calculated based on the activity curves. In addition, tear osmolarity measurements, tear breakup time (tBUT), and Schirmer I (STI) tests were performed prior to DSCI examination. ResultsThe T½ values were 29.91 ± 11.61 min in MGD patients and 6.26 ± 1.5 min in healthy controls. Tear osmolarity parameters were 308 ± 9.41 mOsm/L and 288.9 ± 6.4 mOsm/L, tBUT values were 5.54 ± 2.73 s and 11.4 ± 2.7 s, while the STI test values were 6.17 ± 2.78 mm and 13.58 ± 3.8 mm, respectively. The differences were significant (p < 0.01) in all cases. ConclusionsAlthough the MGD patients’ lacrimal drainage systems were patent their tear clearance values were significantly higher than those of healthy volunteers, which may be caused by decreased drainage of tears from the eyes towards the nasal cavity. The understanding of new features regarding the altered physico-chemical characteristics of MGD tears has been augmented by the results of this study.

Preclinical Evaluation of 99mTc-Ethambutol, an Alternative Tuberculosis Diagnostic Tool

99mTc-ethambutol was preclinically evaluated as an alternative diagnostic tuberculosis agent. Its radiochemical purity, stability in saline and serum, in vitro Mycobacterium tuberculosis (MBT) binding, and biodistribution in mice were studied, and targeted imaging in model rabbits was performed. The following labeling conditions were found to be optimum: 3 mg of EMB, 150 µg of stannous fluoride, 3 mCi of sodium pertechnetate, pH 5.6. The highest product yield was reached in the time interval 30–90 min after reconstitution. The relative content of 99mTc-EMB in normal saline at room temperature decreased to 90 ± 0.25% in 240 min. 99mTc-EMB was stable in vitro in serum at 37°C, with 16.8 ± 0.3% radioimpurities accumulated in 16 h. 99mTc-EMB showed 69.8 ± 1.5% in vitro uptake in live strains of MBT. High in vivo accumulation (15.5 ± 0.8% ID) of the labeled EMB was observed in the infected site of model mice as compared to the normal and inflamed (muscles) sites. High uptake in the MBT infected site of a model rabbit was seen scintigraphically at 120 min after the intravenous administration of the 99mTc-EMB. Stability in normal saline and serum, substantial in vitro MBT uptake, high in vivo accumulation in the infected site, and accurate scintigraphy of the infected site make 99mTc-EMB promising as a novel alternative diagnostic tool for tuberculosis.

Qualitative and quantitative scintigraphy in sialorrhea before and after botulinum toxin injection

Sialorrhea is excessive saliva production and its usual escape of from the oral cavity. The use of botulinum toxin has been preconized, but its effectiveness until now has been unreliably measured. Our objective was to qualitatively and quantitatively determine the effectiveness of botulinum toxin injection in the reduction of saliva production by the parotid gland. Outcomes research. Patients with moderate-to-critical sialorrhea had one of the parotid glands injected with 50 U of botulinum toxin, leaving the other as the control. Fifteen days after the toxin injection, they underwent scintigraphic analyses with intravenous injection of 10 mCi (37 MBq) of Tc-99 m (sodium pertechnetate). After this, the noninjected gland was treated for therapeutic complementation. The glands injected with botulinum toxin showed uptake reduction in 100% of patients. The uptake reduction in counts per second varied from 8% to 36%. The Wilcoxon paired test comparing the control glands with those injected showed a significant difference for the action of botulinum toxin (P = .0039). The scintigraphic study of parotid glands shows that botulinum toxin is effective in reducing sodium pertechnetate uptake. 2c Laryngoscope, 129:2521-2526, 2019.

Technetium-99m radiolabeling and biological study of epirubicin for in vivo imaging of multi-drug-resistant Staphylococcus aureus infections via single photon emission computed tomography.

The development of functional imaging is a promising strategy for diagnosis and treatment of infectious and cancerous diseases. In this study, epirubicin was developed as a [99m Tc]-labeled radiopharmaceutical for the imaging of multi-drug-resistant Staphylococcus aureus infections. The labeling was carried out using sodium pertechnetate (Na99m TcO4 ; ~370MBq). The other parameters such as amount of ligand, reducing agent (SnCl2 .2H2 O), and pH were optimized. The highest labeling yield ≥96.98% was achieved when 0.3mg epirubicin, 13μg SnCl2 .2H2 O, and ~370MBq Na99m TcO4 were incubated at pH 7 for 15min in the presence of ascorbic acid at room temperature. Radiochemical purity, stability, charge, and glomerular filtration rate were studied to evaluate the biological compatibility for in vivo administration. Biodistribution investigations showed radiotracer uptake (13.89±1.56%ID/gm organ) by liver and 7.79±0.38%ID/gm organ by kidneys at 30min post-injection which promisingly wash out at 24hr post-injection. Scintigraphy study showed selective uptake in S.aureus-infected tissues in contrast to turpentine oil-induced inflamed tissues. Target-to-non-target ratio (6.7±0.05) was calculated at 1hr post-injection using SPECT gamma camera. The results of this study reveal that the [99m Tc]-epirubicin can be a choice of imaging and monitoring the treatment process of multi-drug resistant S.aureus bacterial infections.

Effect of sphere size and reconstruction method on 99Tcm-pertechnetate SPECT/CT imaging: a phantom study

Objective To validate the quantitative accuracy of 99Tcm-pertechnetate(99TcmO4-)SPECT/CT imaging and its influencing factors (sphere size, radioactive concentration, reconstruction methods). Methods National Electrical Manufacturers Association (NEMA) International Electrotechnical Commission (IEC) body phantom with 99TcmO4- solution filled in 6 spheres (diameter: 10, 13, 17, 22, 28, 37 mm) and 1 cylinder (target/background ratio: 10∶1) was used to assess the accuracy of uptake quantification. SPECT/CT was used for imaging data acquisition, and volume of interest (VOI) was drawn after the images being corrected and reconstructed. The radioactive concentrations of 6 spheres were measured and compared with the true radioactive concentrations, and quantitative accuracy of each sphere was calculated. The experiment was repeated for 12 times with the same method and different radioactive concentrations. Ordered-subsets expectation maximization (OSEM) reconstruction was performed with 2 or 5 iterations to process imaging data. CT VOI and nuclear medicine (NM) threshold methods were used for the delineation of VOI. Accuracy was compared by paired t test. Results The NM thresholds to get calculated volume close to the true volume were determined to be 40%, 40%, 50%, 70%, 80%, 90% for 6 spheres with diameters of 37, 28, 22, 17, 13, 10 mm, respectively. Comparing 2 methods of VOI delineation (CT VOI and NM threshold), only the accuracy for 17 mm sphere was significantly different (t=5.89, P<0.01). Five iterations group showed higher accuracy than 2 iterations group (t values: 3.19-6.92, all P<0.05). The average accuracies under 12 different radioactive concentrations were 102%, 95%, 80%, 66%, 27%, 20%, respectively, for spheres in order from large size to small size. Conclusion The sphere volume and reconstruction method have effect on quantitative accuracy of 99TcmO4- SPECT/CT imaging, and spheres smaller than 17 mm is also significantly affected by partial volume effect. Key words: Tomography, emission-computed, single-photon; Tomography, X-ray computed; Models, structural; Image processing, computer-assisted; Sodium pertechnetate Tc 99m

Salivary gland dynamic imaging for salivary gland damage in Sjogren′s syndrome patients with normal Young′s modulus value

Objective To evaluate the damage of the salivary gland in Sjogren′s syndrome (SS) patients with normal Young′s modulus value (YMV) using salivary gland dynamic imaging (SGDI). Methods A total of 78 parotid glands and submandibular glands of SS patients and 100 parotid glands and submandibular glands of healthy people were collected in this retrospective study. The difference of YMV between 2 groups was analyzed with two-sample t test; receiver operating characteristic (ROC) curves of YMV were drawn to calculate the area under carve (AUC) and cut-off values. SGDI was used to observe the uptake ratio of 15 min (UR15) value in the SS salivary glands with normal YMV. Results The YMV of left parotid/submandibular glands and right parotid/submandibular glands were not statistically different in both SS patients and healthy people (t values: from -1.192 to -0.404, all P>0.05). The YMV of parotid/submandibular glands in SS patients was higher than that in healthy people: (15.39±8.08) vs (9.33±2.21) kPa, (14.35±5.33) vs (9.18±2.36) kPa (t values: 7.169 and 8.662, both P 0.05). The UR15 value of 78 SS parotid glands and submandibular glands were 1.42±0.97 and 1.19±0.83, respectively. About 58.33%(14/24) parotid glands with normal YMV (<10.85 kPa) and 76.19% (16/21) submandibular glands with normal YMV (<10.95 kPa) had reduced cellular uptake in SS patients. Conclusions Parotid glands and submandibular glands in SS patients are damaged, and the tissue hardness is increased. SGDI can discover the cellular damage in SS salivary glands with normal YMV. Key words: Sjogren′s syndrome; Parotid gland; Submandibular gland; Radionuclide imaging; Sodium pertechnetate Tc 99m