Diagnostic testing for Graves' or non-Graves' hyperthyroidism: A comparison of two thyrotropin receptor antibody immunoassays with thyroid scintigraphy and ultrasonography.

OBJECTIVE: Graves' disease (GD) is the most common cause of hyperthyroidism. In many cases, when the aetiological diagnosis of GD is not evident based on the clinical evaluation and thyroid function testing, it may become challenging to distinguish Graves' hyperthyroidism from other forms of thyrotoxicosis. The current study was primarly carried out to compare the diagnostic effectiveness of two TSH receptor antibody immunoassays (IMAs), ultrasonography and thyroid scintigraphy in hyperthyroidism scenario. METHODS: We retrospectively analysed consecutive patients with newly diagnosed and untreated thyrotoxicosis who underwent thyroid functional tests, both TRAb and TSI measurements, thyroid scintigraphy and ultrasonography. TRAb assessment was carried out by Kryptor® compact PLUS, while TSI by Immulite® . Echo pattern 3 corresponded to 'thyroid inferno', and the final diagnosis of GD vs non-Graves' hyperthyroidism was made according to the thyroid scan (qualitative scintigraphy). Receiver operating characteristic (ROC) curves were drawn using the final diagnosis as reference. Clinical sensitivity and specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for all the tests. RESULTS: A total of 124 untreated hyperthyroid patients were included in our study (GD, n = 86 vs non-Graves' hyperthyroidism, n = 38). ROC curves showed that the optimal cut-off values associated with the highest diagnostic sensitivity and specificity was 0.7 IU/L for TRAb Kryptor® (93 [85.4-97.4] and 86.8 [71.9-95.5]) and 0.1 IU/L for TSI Immulite® (94.2 [86.9-98.1] and 84.2 [68.7-93.9]), respectively. For the echo pattern 3, we found a good sensitivity (92.1%) and a high PPV (95.2%) but a quite low specificity value (69.8%) and a relative low NPV (57.5%). For thyroid scintigraphy, the TcTU cut-off value of 1.3% corresponded to the best limit for sensitivity and specificity in our patients (95.3 [88.5-98.7] and 96.4 [81.6-99.4]). The Passing-Bablok regression equation and the Bland-Altman test showed a great degree of correlation and agreement existed between TRAb Kryptor® and Immulite® TSI results. CONCLUSIONS: Thyroid scintigraphy remains the most accurate method to differentiate causes of thyrotoxicosis. However, TRAb assays can be alternatively adopted in this setting, limiting the use of thyroid scintigraphy (TcTU evaluation) to TRAb-negative patients. Thyoid US is less accurate than both TRAb/TSI and thyroid scintigraphy, but the 'thyroid inferno' pattern provides a high PPV for GD.

Scintigraphic peritoneography reveals a non-uniform 99mTc-Pertechnetat aerosol distribution pattern for Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) in a swine model.

BACKGROUND: Although recent data are contradictory, it is still claimed that Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) would deliver an aerosol which distributes homogeneously throughout the entire abdominal cavity. METHODS: 99mTc-Pertechnetat was administered in four postmortem swine using either PIPAC or liquid intra-peritoneal chemotherapy (IPC). The animals were examined by planar scintigraphy and SPECT/CT. Planar distribution images were divided into four regions of interest (ROIs: right/left upper and lower abdominal quadrant). SPECT/CT slices were scanned for areas of intense nuclide accumulation ("hot spots"). The percentage of relative distribution for planar scintigraphy was calculated by dividing the summed individual counts of each ROI by total counts measured in the entire abdominal cavity. The relative distribution of the "hot spots" was analyzed by dividing the counts of the local volume of interest (VOI) by the summed volume counts measured in the entire abdominal cavity. RESULTS: In all four animals, planar scintigraphy showed inhomogeneous nuclide distribution. After PIPAC only 8-10% of the delivered nuclide was detected in one ROI with a mean deviation of 40% and 74% from a uniform nuclide distribution pattern. In all animals, SPECT/CT revealed "hot spots" beneath the PIPAC Micropump, catheter tip, and in the cul-de-sac region which comprise about 25% of the total amount of delivered nuclide in 2.5% of the volume of the entire abdominal cavity. CONCLUSIONS: Our present data indicate that the intra-abdominal aerosol distribution pattern of PIPAC therapy is non-homogeneous and that the currently applied technology has still not overcome the problem of inhomogeneous drug distribution of IPC.

PREDICTION OF RELAPSE FROM HYPERTHYROIDISM FOLLOWING ANTITHYROID MEDICATION WITHDRAWAL USING TECHNETIUM THYROID UPTAKE SCANNING.

OBJECTIVE: Technetium thyroid uptake (TTU) is not inhibited by antithyroid drugs (ATD) and reflects the degree of thyroid stimulation. We intended to predict the relapse rate from hyperthyroidism based on TTU measurement. METHODS: Out of 44 initially enrolled subjects, 38 patients aged 41.6 ± 14.6 with Graves disease (duration: 84 ± 78 months) completed the study. TTU was performed with 40-second imaging of the neck and mediastinum 20 minutes after injection of 1 mCi technetium-99m pertechnetate. TTU was measured as the percentage of the count of activity accumulated in the thyroidal region minus the mediastinal background uptake to the count of 1 mCi technetium-99m under the same acquisition conditions. Then methimazole was stopped and patients were followed. The optimal TTU cutoff value for Graves relapse prediction was calculated using Youden's J statistic. RESULTS: Hyperthyroidism relapsed in 11 (28.9%) patients 122 ± 96 (range: 15-290) days post-ATD withdrawal. The subjects in remission were followed for 209 ± 81 days (range: 88-390). TTU was significantly higher in patients with forthcoming relapse (12.0 ± 8.0 vs. 3.9 ± 2.0, P = .007). The difference was significant after adjustment for age, sex, history of previous relapse, disease duration, and thyroid-stimulating hormone (TSH) levels before withdrawal. The area under the receiver operative characteristic (ROC) curve was 0.87. The optimal TTU cutoff value for classification of subjects with relapse and remission was 8.7 with sensitivity, specificity, and positive and negative predictive value of 73%, 100%, 100%, and 90%, respectively (odds ratio [OR] = 10.0; 95% confidence interval [CI]: 3.4-29.3). CONCLUSION: TTU evaluation in hyperthyroid patients receiving antithyroid medication is an accurate and practical method for predicting relapse after ATD withdrawal. ABBREVIATIONS: ATD = antithyroid drugs RIU = radio-iodine uptake TSH = thyroid-stimulating hormone TSI = thyroid-stimulating immunoglobulin TTU = technetium thyroid uptake.

Small-Animal SPECT/CT of the Progression and Recovery of Rat Liver Fibrosis by Using an Integrin αvß3-targeting Radiotracer.

PURPOSE: To assess the potential utility of an integrin αvß3-targeting radiotracer, technetium 99m-PEG4-E[PEG4-cyclo(arginine-glycine-aspartic acid-D-phenylalanine-lysine)]2 ((99m)Tc-3PRGD2), for single photon emission computed tomography (SPECT)/computed tomography (CT) for monitoring of the progression and prognosis of liver fibrosis in a rat model. MATERIALS AND METHODS: All animal experiments were performed by following the protocol approved by the institutional animal care and use committee. (99m)Tc-3PRGD2 was prepared and longitudinal SPECT/CT was performed to monitor the progression (n = 8) and recovery (n = 5) of liver fibrosis induced in a rat model by means of thioacetamide (TAA) administration. The mean liver-to-background radioactivity per unit volume ratio was analyzed for comparisons between the TAA and control (saline) groups at different stages of liver fibrosis. Data were compared by using Student t and Mann-Whitney tests. Results:of SPECT/CT were compared with those of ex vivo biodistribution analysis (n = 5). RESULTS: Accumulation of (99m)Tc-3PRGD2 in the liver increased in proportion to the progression of fibrosis and TAA exposure time; accumulation levels were significantly different between the TAA and control groups as early as week 4 of TAA administration (liver-to-background ratio: 32.30 ± 3.39 vs 19.01 ± 3.31; P = .0002). Results of ex vivo immunofluorescence staining demonstrated the positive expression of integrin αvß3 on the activated hepatic stellate cells, and the integrin αvß3 levels in the liver corresponded to the results of SPECT/CT (R(2) = 0.75, P < .0001). (99m)Tc-3PRGD2 uptake in the fibrotic liver decreased after antifibrotic therapy with interferon α2b compared with that in the control group (relative liver-to-background ratio: 0.45 ± 0.05 vs 1.01 ± 0.05; P < .0001) or spontaneous recovery (relative liver-to-background ratio: 0.56 ± 0.06 vs 1.01 ± 0.05; P < .0001). CONCLUSION: (99m)Tc-3PRGD2 SPECT/CT was successfully used to monitor the progression and recovery of liver fibrosis and shows potential applications for noninvasive diagnosis of early stage liver fibrosis.

Cutoff value of thyroid uptake of (99m)Tc-pertechnetate to discriminate between Graves' disease and painless thyroiditis: a single center retrospective study.

Thyroid uptake of (99m)Tc-pertechnetate is a useful way to determine the cause of thyrotoxicosis. In daily clinical practice, (99m)Tc-pertechnetate uptake is used to discriminate between Graves' disease and painless thyroiditis when clinical information is not enough to make the distinction. However, since the optimal cutoff value of (99m)Tc-pertechnetate uptake has not yet been elucidated, our aim was to determine this value. We recruited patients with thyrotoxicosis in whom (99m)Tc-pertechnetate uptake was measured in clinical settings between 2009 and 2013. Three experienced endocrinologists (who were blinded to the value of (99m)Tc-pertechnetate uptake and initial treatment) diagnosed the cause of thyrotoxicosis based on thyrotropin, free triiodothyronine, free thyroxine, and thyrotropin receptor antibody levels, and by ultrasound findings and using images of thyroid uptake of (99m)Tc-pertechnetate without the actual values. Ninety-four patients diagnosed as having Graves' disease or painless thyroiditis were finally included. According to the diagnosis, the optimal cutoff value of (99m)Tc-pertechnetate uptake was determined by receiver operating characteristics analysis. A cutoff value of 1.0% provided optimal sensitivity and specificity of 96.6% and 97.1%, respectively. Then, its validity was confirmed in 78 patients with confirmed Graves' disease or painless thyroiditis diagnosed at another institute. Applying this cutoff value to the patients with thyrotoxicosis revealed positive and negative predictive values for Graves' disease of 100% and 88.9%, respectively. In conclusion, a cutoff value for (99m)Tc-pertechnetate uptake of 1.0% was useful to discriminate between Graves' disease and painless thyroiditis.

99mTc-zolmitriptan: radiolabeling, molecular modeling, biodistribution and gamma scintigraphy as a hopeful radiopharmaceutical for lung nuclear imaging.

Lung imaging radiopharmaceuticals are helpful agents for measuring pulmonary blood flow and allow detection of pulmonary embolism and lung cancer. The goal of this study was to develop a novel potential radiopharmaceutical for lung imaging. Zolmitriptan (a selective serotonin receptor agonist) was successfully labeled with 99mTc via direct labeling method under reductive conditions studying different factors affecting the labeling efficiency. 99mTc-zolmitriptan was obtained with a maximum labeling yield of 92.5 ± 0.61 % and in vitro stability up to 24 h. Molecular modeling was done to predict the structure of 99mTc-zolmitriptan and ensure that radiolabeling did not affect binding ability of zolmitriptan to its receptor. Biodistribution studies showed that maximum lung uptake of 99mTc-zolmitriptan was 23.89 ± 1.2 % injected dose/g tissue at 15 min post-injection and retention in lungs remained high up to 1 h, whereas the clearance from mice appeared to proceed mainly via the renal pathway. Scintigraphic images confirmed the biodistribution results showing a high resolution lung image with low accumulation of radioactivity in other organs except kidneys and urinary bladder. 99mTc-zolmitriptan is not a blood product and so it is more safe than the currently available 99mTc-MAA, and its lung uptake is higher than that of the recently discovered 123I-IPMPD, 99mTc(CO)5I and 99mTc-DHPM. So, 99mTc-zolmitriptan could be used as a hopeful radiopharmaceutical for lung scintigraphic imaging.

Increased pertechnetate and radioiodine uptake in the thyroid gland with subacute thyroiditis and concurrent Graves' disease.

OBJECTIVE: A 61 years old woman presented with low grade fever and weight loss for a month. Thyroid function tests showed hyperthyroidism: increased technetium-99m pertechnetate ((99m)Tc O(-)4) and radioiodine ((131)I) uptake and elevated thyroid stimulating hormone receptor antibodies (TSHRAb). She also had high erythrocyte sedimentation rate. Fine-needle aspiration (FNA) biopsies of left thyroid lobe revealed subacute thyroiditis (SAT). Simultaneous occurrence of SAT and Graves' disease (GD) was diagnosed. The patient was in good physical condition after two doses of betamethasone and daily administration of low dose antithyroid drugs. CONCLUSION: This case indicated that the measurement of TSHRAb is useful in understanding the clinical course of patients with SAT when thyroid function tests including the (99m)Tc and (131)I uptake are not compatible with the diagnosis. In such cases, GD should be suspected. The mechanism of high (99m)Tc and/or (131)I uptake in patients with simultaneous SAT and GD may be due to the inflammatory process which was detected by FNA in a small part of the left thyroid lobe inducing the stimulating effects of elevated TSHRAb on the undamaged follicular cells.

A biokinetic model for systemic technetium in adult humans.

This paper reviews biokinetic data for technetium and proposes a biokinetic model for systemic technetium in adult humans. The development of parameter values focuses on data for pertechnetate TcO(-)(4) the most commonly encountered form of technetium and the form expected to be present in body fluids. The model is intended as a default model for occupational or environmental intake of technetium, i.e. applicable in the absence of form- or site-specific information. Tissues depicted explicitly in the model include thyroid, salivary glands, stomach wall, right colon wall, liver, kidneys, and bone. Compared with the ICRP's current biokinetic model for occupational or environmental intake of technetium (ICRP 1993, 1994), the proposed model provides a more detailed and biologically realistic description of the systemic behaviour of technetium and is based on a broader set of experimental and medical data. For acute input of (99m)Tc (T(1/2) = 6.02 h) to blood, the ratios of cumulative (time-integrated) activity predicted by the current ICRP model to that predicted by the proposed model range from 0.4-7 for systemic regions addressed explicitly in both models. For acute input of (99)Tc (T(1/2) = 2.1 × 10(5) year) to blood, the corresponding ratios range from 0.2-30.

Construction and radiolabeling of adenovirus variants that incorporate human metallothionein into protein IX for analysis of biodistribution.

Using adenovirus (Ad)-based vectors is a promising strategy for novel cancer treatments; however, current tracking approaches in vivo are limited. The C-terminus of the Ad minor capsid protein IX (pIX) can incorporate heterologous reporters to monitor biodistribution. We incorporated metallothionein (MT), a low-molecular-weight metal-binding protein, as a fusion to pIX. We previously demonstrated 99mTc binding in vitro to a pIX-MT fusion on the Ad capsid. We investigated different fusions of MT within pIX to optimize functional display. We identified a dimeric MT construct fused to pIX that showed significantly increased radiolabeling capacity. After Ad radiolabeling, we characterized metal binding in vitro. We explored biodistribution in vivo in control mice, mice pretreated with warfarin, mice preimmunized with wild-type Ad, and mice that received both warfarin pretreatment and Ad preimmunization. Localization of activity to liver and bladder was seen, with activity detected in spleen, intestine, and kidneys. Afterwards, the mice were euthanized and selected organs were dissected for further analysis. Similar to the imaging results, most of the radioactivity was found in the liver, spleen, kidneys, and bladder, with significant differences between the groups observed in the liver. These results demonstrate this platform application for following Ad dissemination in vivo.

The Diagnostic Utility of Color Doppler Ultrasonography, Tc-99m Pertechnetate Uptake, and TSH-Receptor Antibody for Differential Diagnosis of Graves' Disease and Silent Thyroiditis: A Comparative Study.

OBJECTIVE: The differential diagnosis of Graves disease (GD) and silent thyroiditis (ST) is important for the selection of appropriate treatment. To date, no study has compared the diagnostic utility of color Doppler ultrasonography (CDUSG), Tc-99m (technetium-99m) pertechnetate uptake, and thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) for the differential diagnosis of these two conditions. In the present study, we compared the diagnostic utility of inferior thyroid artery (ITA) peak systolic and end diastolic velocities (PSV and EDV) measured by CDUSG, Tc-99m pertechnetate uptake, and TRAb for differential diagnosis of GD and ST. METHODS: A total of 150 subjects with GD, 79 with ST, and 71 healthy euthyroid controls were included in the study. Diagnoses of GD and ST were made according to patient signs and symptoms, physical examination findings, the results of TRAb and Tc-99m pertechnetate uptake, and follow-up findings. All subjects underwent CDUSG for the quantitative measurement of ITA blood-flow velocities. RESULTS: The mean ITA-PSV and EDV in patients with GD were significantly higher than in ST patients. In receiver operating characteristic analysis, the sensitivity/specificity of the 30 and 13.2 cm/s cutoff values of the mean ITA-PSV and EDV for discrimination of GD from ST were 95.3/94.9% and 89.3/88.6%, respectively. The sensitivity/specificity of the 1.0 international unit (IU)/L and 3% cutoff values of the TRAb and Tc-99m pertechnetate uptake analyses were 93.0/91.0% and 90.7/89.9%, respectively. CONCLUSION: The measurement of ITA-PSV by CDUSG is a useful diagnostic tool and is a complementary method to the TRAb and Tc-99m pertechnetate uptake methods for differential diagnosis of GD and ST.

¹¹¹Indium-labeled ultrafine carbon particles; a novel aerosol for pulmonary deposition and retention studies.

Continuous environmental or occupational exposure to airborne particulate pollution is believed to be a major hazard for human health. A technique to characterize their deposition and clearance from the lungs is fundamental to understand the underlying mechanisms behind their negative health effects. In this work, we describe a method for production and follow up of ultrafine carbon particles labeled with radioactive ¹¹¹Indium (¹¹¹In). The physicochemical and biological properties of the aerosol are described in terms of particle size and concentration, agglomeration rate, chemical bonding stability, and human lung deposition and retention. Preliminary in vivo data from a healthy human pilot exposure and 1-week follow up of the aerosol is presented. More than 98% of the generated aerosol was labeled with Indium and with particle sizes log normally distributed around 79 nm count median diameter. The aerosol showed good generation reproducibility and chemical stability, about 5% leaching 7 days after generation. During human inhalation, the particles were deposited in the alveolar space, with no central airways involvement. Seven days after exposure, the cumulative activity retention was 95.3%. Activity leaching tests from blood and urine samples confirmed that the observed clearance was explained by unbound activity, suggesting that there was no significant elimination of ultrafine particles. Compared to previously presented methods based on Technegas, ¹¹¹In-labelled ultrafine carbon particles allow for extended follow-up assessments of particulate pollution retention in healthy and diseased lungs.

Blood flow to the extensor carpi radialis brevis muscle following adrenaline infusion in patients with lateral epicondylitis.

PURPOSE: Based on previous evidence of muscle fiber injury and decreased blood flow in the extensor carpi radialis brevis (ECRB) muscle in lateral epicondylitis (LE), we hypothesized that there would also be an abnormal (vasoconstrictive) vascular response to adrenaline in the ECRB muscle in LE. METHODS: In a case-control study, we measured skeletal muscle blood flow in 8 patients with LE and in 8 healthy controls in response to a 30-minute intravenous infusion of adrenaline. We used local clearance of technetium-99m in the main portion of the ECRB muscle to calculate muscle blood flow. RESULTS: In support of the hypothesis, the blood flow response to the adrenaline infusion was markedly different in the 2 study groups. Whereas the continuous decrease in technetium-99m clearance rate over time was interrupted by the adrenaline-induced vasodilatory effect in the control group, we detected no such effect in the patient group. CONCLUSIONS: In the ECRB muscle in LE, there is a shift in the balance of vasodilatory and vasoconstrictory influences of adrenaline, leading to vasoconstriction during low-dose adrenaline infusion. The adverse adrenaline effect is similar to what was previously observed after minor muscle injury. Whether the vasoregulatory change, by causing relative muscle ischemia, represents the primary etiology in LE or results from muscle injury cannot be determined, but it is likely to contribute to the development and continuation of chronic muscle pain in LE. New ways of thinking about the condition may be required, and pharmacological treatment might be an option to improve the blood supply and avoid further damage to the affected ECRB muscle-tendon unit.

[99mTc reduces clonogenic survival after intracellular uptake in NIS-positive cells in vitro more than 131I]. / 99mTc reduziert nach intrazellulärer Aufnahme in NIS-positiven Zellen in vitro das klonogene Uberleben stärker als 131I.

AIM: In addition to gamma radiation of 140 keV 99mTc emits during the transition to 99Tc electrons of low energy and tiny path-lengths. These Auger electrons cannot be utilized in diagnostic procedures. However, they were discussed frequently for therapeutic application. Hitherto proof of effect of the Auger electrons from 99mTc is missing which is supplied now in an in vitro-system in comparison to beta-emitter 131I. METHODS: The thyroid cell line PCCl3 (sodium iodide symporter (NIS)-positive) was incubated with 131I-sodium iodide (131I) or 99mTc-pertechnetate (99mTc) in presence or absence of perchlorate. For comparison the amount of radioactivity was adjusted to obtain the same dose from extracellular irradiation for both radionuclides. The colony forming assay detects the clonogenic cell survival as surviving fraction. In addition, intracellular radionuclide uptake was quantified. RESULTS: Dose effect curves were established for 131I and 99mTc for variable extra- and intracellular distribution of the radioactivity. In presence of perchlorate no cellular uptake of radioactivity was detectable. Survival curves were largely comparable confirming the dosimetric calculations. In absence of perchlorate cellular radiotracer uptake varied from 1.39% (131I) to 1.90% 99mTc). Effects on survival were twice for the beta-emitter and ten-fold higher for 99mTc. CONCLUSIONS: Intracellular uptake of 131I and 99mTc increases DNA-damage compared to strict extracellular radiotracer distribution which was demonstrated by means of colony forming assay. Increasing radiotoxicity from intracellular 99mTc is explained most likely by increased dose deposition in cellular structures due to Auger- and conversion-electrons of low range and high local energy deposition.

Systemic absorption of Tc-99m-pertechnetate during dacryoscintigraphy: a note of caution.

We report a 37-year-old patient with the history of bilateral epiphora, who was referred to our department for dacryoscintigraphy imaging. The patient had bilateral obstruction of the lacrimal apparatus at the sac-duct level on the scintigraphy images. Delayed imaging showed Tc-99m pertechnetate uptake in the thyroid due to systemic absorption of the tracer from the conjunctiva. We recommend using tracers with large particle size and lower possibility of mucosal absorption for dacryoscintigraphy in order to decrease unnecessary thyroid radiation.

Enhanced noninvasive imaging of oncology models using the NIS reporter gene and bioluminescence imaging.

Noninvasive bioluminescence imaging (BLI) of luciferase-expressing tumor cells has advanced pre-clinical evaluation of cancer therapies. Yet despite its successes, BLI is limited by poor spatial resolution and signal penetration, making it unusable for deep tissue or large animal imaging and preventing precise anatomical localization or signal quantification. To refine pre-clinical BLI methods and circumvent these limitations, we compared and ultimately combined BLI with tomographic, quantitative imaging of the sodium iodide symporter (NIS). To this end, we generated tumor cell lines expressing luciferase, NIS, or both reporters, and established tumor models in mice. BLI provided sensitive early detection of tumors and relatively easy monitoring of disease progression. However, spatial resolution was poor, and as the tumors grew, deep thoracic tumor signals were massked by overwhelming surface signals from superficial tumors. In contrast, NIS-expressing tumors were readily distinguished and precisely localized at all tissue depths by positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging. Furthermore, radiotracer uptake for each tumor could be quantitated noninvasively. Ultimately, combining BLI and NIS imaging represented a significant enhancement over traditional BLI, providing more information about tumor size and location. This combined imaging approach should facilitate comprehensive evaluation of tumor responses to given therapies.

RADIOISOTOPE DIAGNOSTIC ALGORITHM FOR THE RELAPSE AND METASTASES DETECTION IN THE IODINE-NEGATIVE DIFFERENTIATED THYROID CANCER. / RADIONUKLIDNYI DIAGNOSTYChNYI ALGORYTM DLIa VYIaVLENNIa RETsYDYVIV I METASTAZIV U KhVORYKh Z IOD-NEGATYVNYMY FORMAMY DYFERENTsIIOVANOGO RAKU ShchYTOPODIBNOÏ ZALOZY.

OBJECTIVE: Developing of algorithm for the post-surgical management of patients with iodine-negative metastasesof differentiated thyroid cancer (DTC). MATERIALS AND METHODS: The DTC patients with iodine-negative metastases (n = 115) were enrolled in the study.Of them the whole body scintigraphy (WBS) was performed with technetium-99m-hexakis-2-methoxyisobutylisonitrile(99mTc-MIBI) (n = 30), WBS with technetium-99m dimercaptosuccinic acid (99mTc-DMSA) (n = 30), 18FDG PET (n = 30), andcomputer tomography (CT-scan) (n = 25). Complex 99mTc-pertechnetate scans including the dynamic and static scintigraphy was performed supplementary to 99mTc-MIBI WBS in 10 patients to obtain the angiographic curves from DTCmetastatic foci. The non-radioiodine radiopharmaceutical technologies, namely the labeled 99mTc-MIBI, 99mTc-DMSA, 99mTc-pertechnetate, and 18FDG were applied to detect the iodine-negative DTC metastases. Radioisotopic examinationswere performed at the dual-head gamma camera (Mediso Medical Imaging Systems Ltd., Hungary) and single photonemission computed tomography (SPECT) scanner «E.CAM¼ (Siemens, Germany). PET/CT scans were performed on the«Biograph 64 TruePoint¼ imaging platform (Siemens, Germany) in accordance with the European Association of NuclearMedicine (EANM) recommendations for the Siemens imaging devices with 3D-mode data acquisition. RESULTS: The conducted research suggested that it is feasible to use the non-radioiodine (99mTc-MIBI and 99mTc-DMSA)radiopharmaceutical technologies to detect the iodine-negative DTC metastases. 18FDG PET is a highly informativetechnology for the detection of iodine-negative DTC metastases in case of lung involvement in the process. Compareof the non-radioiodine radiopharmaceuticals, CT scan and 18FDG-PET/CT indicated the highest sensitivity of 18FDGPET/CT (p < 0.05). WBS with 99mTc-MIBI and 99mTc-DMSA featured the highest specificity (100 %, p < 0.05). X-ray CTis marked by the significantly lower either sensitivity, specificity, and accuracy rate (p > 0.05). Developing andapplication of algorithm for the post-surgical management of patients with iodine-negative forms of DTC will allowfor the betimes detection of relapses and metastases with administration of adequate surgical, radiation, and targeted treatment. CONCLUSIONS: Obtained results offer the opportunity to optimize the post-surgical management of patients withiodine-negative DTC forms using the options of radionuclide diagnostics with non-radioiodine radiopharmaceuticals. The latter are readily available providing the cost-cutting of diagnostic support in these patients. Place ofmorphological methods of diagnosis is determined and stage of monitoring of patients with the iodine-negativemetastases is established. Possibility of the 18FDG-PET tests for the early diagnosis of iodine-negative metastases inDTC for the first time have been studied and substantiated in Ukraine. A comprehensive radiation algorithm for thelong-term monitoring of this category of patients will allow the timely detection of recurrences and metastases ofDTC and appropriate surgery, radiation and targeted therapy administration. Data obtained as a result of the studyallowed to improve the overall and recurrence-free survival rates in the able-bodied DTC patients and reduce thecosts of follow-up of patients with iodine-negative forms of DTC.

2009 EANM parathyroid guidelines.

The present guidelines were issued by the Parathyroid Task Group of the European Association of Nuclear Medicine. The main focus was imaging of primary hyperparathyroidism. Dual-tracer and single-tracer parathyroid scintigraphy protocols were discussed as well as the various modalities of image acquisition. Primary hyperparathyroidism is an endocrine disorder with high prevalence, typically caused by a solitary parathyroid adenoma, less frequently (about 15%) by multiple parathyroid gland disease (MGD) and rarely (1%) by parathyroid carcinoma. Patients with MGD may have a double adenoma or hyperplasia of three or all four parathyroid glands. Conventional surgery has consisted in routine bilateral neck exploration. The current trend is toward minimally invasive surgery. In this new era, the success of targeted parathyroid surgery depends not only on an experienced surgeon, but also on a sensitive and accurate imaging technique. Recognizing MGD is the major challenge for pre-operative imaging, in order to not direct a patient towards inappropriate minimal surgery. Scintigraphy should also report on thyroid nodules that may cause confusion with a parathyroid adenoma or require concurrent surgical resection. The two main reasons for failed surgery are ectopic glands and undetected MGD. Imaging is mandatory before re-operation, and scintigraphy results should be confirmed with a second imaging technique (usually US for a neck focus, CT or MRI for a mediastinal focus). Hybrid SPECT/CT instruments should be most helpful in this setting. SPECT/CT has a major role for obtaining anatomical details on ectopic foci. However, its use as a routine procedure before target surgery is still investigational. Preliminary data suggest that SPECT/CT has lower sensitivity in the neck area compared to pinhole imaging. Additional radiation to the patient should also be considered. The guidelines also discuss aspects related to radio-guided surgery of hyperparathyroidism and imaging of chronic kidney disease patients with secondary hyperparathyroidism.

Trypanosoma cruzi: biodistribution of technetium-99m pertechnetate in infected rats.

With the aim of investigating the biodistribution of technetium-99m pertechnetate ((99m)TcO4-) in rats infected with Y strain of Tripanosoma Cruzi, at the peak of parasitemia, (14th day of infection), we injected Wistar rats with 0.1 ml of (99m)TcO4- (3.7MBq). After 60 min, the percentage of radioactivity per gram was counted in several isolated organs and blood, using a gamma counter (1470 Wizard, PerkinElmer Finland). The uptake of (99m)TcO4- increased significantly in blood and decreased in the colon of infected animals (p<0.05). A significant reduction in serum iron and red blood cells and a significant increase in total proteins, leukocytes and lymphocytes in the infected rats were observed, compared with controls (p<0.05). A reduction in muscle layer thickness of the colon and mononuclear inflammation were observed. These results conclusively demonstrate that T. cruzi infection would be associated with changes in the biodistribution of (99m)TcO4- and in colon morphology, with potential clinical implications.

[Osteal scintigraphy in the evaluation of the course of reparative processes after surgical treatment for tuberculous and nonspecific arthritis, by using constrained bone grafting].

Osteal scintigraphy was used to study the course of reparative processes after surgical treatment in 106 patients with large joint lesions, including 76 patients with tuberculous arthritis and their sequels and 30 with nonspecific and dystrophicones before and 2-3 weeks after operations (those with and without articular tissue revascularization (n = 43 and n = 63); mobilizing (n = 64) and stabilizing (n = 42) operations), of them 22 being performed in late periods (1-3 years (n = 16)). It was established that after mobilizing operations with revascularization, the early postoperative period was marked by a significant increase in radionuclide accumulation (by 1.52 times) and after those without revascularization, there was a less significant rise (by 1.34 times); following stabilizing operations with revascularization, hyperfixation was similar before and after surgery whereas following those without revascularization it significantly reduced (by 1.53% in 70% of patients). The late postoperative period was characterized by reduced hyperfixation, which was more evident after mobilizing operations with revascularization. Osteal scintigraphy quantifies the course of reparative processes and determines the efficiency of different operations.

Precise measurement of intradermal fluid delivery using a low activity technetium-99m pertechnetate tracer.

A method was developed and validated to determine the intradermal (ID) fluid delivery potential of several ID devices, including hollow microneedles. The novel method used water soluble technetium-99 m pertechnetate (99mTcO4-) diluted in normal saline to measure the volume of fluid delivered to and remaining in the skin. The fluid that back-flowed to the skin surface and the fluid left on the device surface were also quantified, thus capturing all fluid volumes deposited during intradermal injections. The technique described in this manuscript was used to assess the injection performance of conventional hypodermic needles and hollow microneedles ex vivo using porcine skin and in vivo with a rat model. Since only a small fraction, 1.1%, of the water-soluble tracer remained bound to the skin when applied topically, the technique can be used to differentiate between injected fluid and backflow. Counting of gamma radiation from 99mTcO4- provided sub-nanoliter resolution for volume measurements, making the proposed method powerful, sensitive, and suitable for the assessments of ID injection devices, particularly for vaccine delivery.