Effect of a second nitroimidazole redox centre on the accumulation of a hypoxia marker: synthesis and in vitro evaluation of 99mTc-labeled bisnitroimidazole propylene amine oxime complexes

Up to now, most of the hypoxia markers contain only one nitroimidazole redox centre, such as Oxo[[3,3,9,9-tetramethyl-1-(2-nitro-1H-imidazol-1-yl)-4,8-diazaundecane-2,10-dione dioximato] (3-)-N,N',N″,N″']-technetium ((99m)Tc-1, BMS181321). Introducing a second nitroimidazole redox centre may enhance the hypoxic accumulation of the markers. In the present work, four (99m)Tc-1 (BMS181321, containing one 2-nitroimidazole) analogues, that is, (99m)Tc-2 (containing two 2-nitroimidazoles), (99m)Tc-3 (containing one 4-nitroimidazole), (99m)Tc-4 (containing two 4-nitroimidazoles) and (99m)Tc-5 (containing both a 2-nitroimidazole and a 4-nitroimidazole) were synthesized, and the hypoxic accumulation was evaluated in vitro using murine sarcoma S180 cells. (99m)Tc-3 and (99m)Tc-4 displayed no significant anoxic/normoxic differentials, whereas (99m)Tc-1 (BMS181321), (99m)Tc-2 and (99m)Tc-5 showed high anoxic cellular uptakes. The anoxic uptake of (99m)Tc-2 reached up to 59.0±0.9% at 4h, which was 2.4 times as that of (99m)Tc-1. (99m)Tc-2 displayed high hypoxic accumulation, indicating that introducing a second nitroimidazole redox centre, that is, 2-nitroimidazole, affected the hypoxic accumulation. Consequently, (99m)Tc-2 may serve as a viable candidate for hypoxia marker. This finding may eventually lead to the development of compounds containing multi-redox centres as hypoxia markers.     

A Tc-99m-labeled long chain fatty acid derivative for myocardial imaging

C-11- and I-123-labeled long chain fatty acid derivatives have been reported as useful radiopharmaceuticals for the estimation of myocardial fatty acid metabolism. We have reported that Tc-99m-labeled N-[[[(2-mercaptoethyl)amino]carbonyl]methyl]-N-(2-mercaptoethyl)-6-aminohexanoic acid ([(99m)Tc]MAMA-HA), a medium chain fatty acid derivative, is metabolized by beta-oxidation in the liver and that the MAMA ligand is useful for attaching to the omega-position of fatty acid derivatives as a chelating group for Tc-99m. On the basis of these findings, we focused on developing a Tc-99m-labeled long chain fatty acid derivative that reflected fatty acid metabolism in the myocardium. In this study, we synthesized a dodecanoic acid derivative, MAMA-DA, and a hexadecanoic acid derivative, MAMA-HDA, and performed radiolabeling and biodistribution studies. [(99m)Tc]MAMA-DA and [(99m)Tc]MAMA-HDA were prepared using a ligand-exchange reaction. Biodistribution studies were carried out in normal mice and rats. Then, a high initial uptake of Tc-99m was observed, followed by a rapid clearance from the heart. The maximum heart/blood ratio was 3.6 at 2 min postinjection of [(99m)Tc]MAMA-HDA. These kinetics were similar to those with postinjection of p-[(125)I]iodophenylpentadecanoic acid. Metabolite analysis showed [(99m)Tc]MAMA-HDA was metabolized by beta-oxidation in the body. In conclusion, [(99m)Tc]MAMA-HDA is a promising compound as a long chain fatty acid analogue for estimating beta-oxidation of fatty acid in the heart.     

Effect of eggplant (Solanum melongena) extract on the in vitro labeling of blood elements with technetium-99m and on the biodistribution of sodium pertechnetate in rats.

The use of eggplant has been suggested to treat different diseases. We studied the effect of eggplant extract on the labeling of red blood cells (RBC) and plasma proteins with technetium-99m (Tc-99m) and on biodistribution of sodium pertechnetate (Tc-99m) in rats. Blood was incubated with an eggplant extract (final concentrations 3.12 to 250.00 mg/ml) for 60 min. Then, stannous chloride (SnCl2) (0.06 or 1.2 microg/ml) and Tc-99m, as sodium pertechnetate, were added. Samples of RBC and plasma (P) were separated and also precipitated and soluble (SF) and insoluble (IF) fractions were isolated. The percent of radioactivity (%ATI) in the fractions was calculated. In the biodistribution study, Wistar rats were treated with eggplant extract (300 mg/ml) for 4 weeks, in drinking water. Tc-99m was administered in the rats, after 90 min they were sacrificed and organs and blood were isolated. When 0.06 microg/ml SnCl2 was used, eggplant extract: i/ inhibited the label of RBC (97.14 +/- 2.01 to 52.21 +/- 3.97%ATI), ii/ decreased the labeling in IF-P from 38.79 +/- 11.73 to 5.49 +/- 2.65%ATI, and iii/ diminished the labeling in IF-RBC from 90.04 +/- 2.65 to 46.17 +/- 9.49%ATI. This inhibitory effect was not observed with SnCl2 1.2 microg/ml. In the biodistribution study, the %ATI: i/ increased in the liver from 2.15 +/- 0.54 to 3.11 +/- 1.29 and ii/ in the other organs the Tc-99m uptake was not modified. The uptake of Tc-99m in red blood cells protein (IF-RBC) decreased from 66.62 +/- 19.67 to 31.66 +/- 8.84%. It is possible to suggest that some components of the eggplant extract present an oxidation power able to alter the fixation of the Tc-99m on the blood elements. Moreover, as eggplant is metabolized in the liver, this fact could justify the alteration of the uptake in this organ.     

Asymmetrical nitrido tc-99m heterocomplexes as potential imaging agents for benzodiazepine receptors

The design, synthesis, and biological evaluation of nitrido technetium-99m complexes for imaging benzodiazepine receptors are described. The design was performed by selecting the precursor biologically active substrate desmethyldiazepam, and the reactive metal-containing fragment [(99m)Tc(N)(PXP)](2+) (PXP = diphosphine ligand) as molecular building-blocks for assembling the structure of the final radiopharmaceuticals through the application of the so-called 'bifunctional' and 'integrated' approaches. This required the synthesis of the ligands H(2)BZ1, H(2)C1, and H(2)C2 (Figures 1 and 2) derived from desmethyldiazepam. In turn, these ligands were reacted with [(99m)Tc(N)(PXP)](2+) to afford the complexes [(99m)Tc(N)(PXP)(L)] (L = BZ1, C1, C2). The chemical nature of the resulting Tc-99m radiopharmaceuticals was investigated using chromatographic methods, and by comparison with the analogous complexes prepared with the long-lived isotope Tc-99g and characterized by spectroscopic and analytical methods. Results showed that the complexes [(99m)Tc(N)(PXP)(L)] are neutral and possess an asymmetrical five-coordinated structure in which two different bidentate ligands, PXP and L, are coordinated to the same Tc[triple bond]N core. With the ligand H(2)BZ1, two isomers were obtained depending on the syn or anti orientation of the pendant benzodiazepine group relative to the Tc[triple bond]N multiple bond. Biodistribution studies of Tc-99m complexes were carried out in rats, and affinity for benzodiazepine receptors was assessed through in vitro binding experiments on isolated rat's cerebral membranes using the corresponding Tc-99g complexes.     

Synthesis and biodistribution studies of technetium-99m-labeled aminopeptidase N inhibitor conjugates

Probestin is a potent aminopeptidase N (APN) inhibitor. Four probestin conjugates containing a tripeptide chelator (N₃S) and a PEG₂ linker were synthesized and radiolabeled with Tc-99m. The number of –COOH groups on the chelator was altered to increase the excretion of the radiotracer from blood stream via the renal-urinary pathway and to decrease its hepatobiliary uptake. Biodistribution of the radiolabeled conjugates was evaluated in healthy CF-1? mice at 1 h post-injection. The results revealed that the Tc-99m labeled probestin conjugate preferentially (>85% injected dose) excreted via the renal route when an aspartic acid residue was added to the linker (conjugate 4). These results suggest that the pharmacokinetic properties of probestin-based APN-targeted agents could be optimized by adding an appropriate amino acid residue in between the linker and the payload.     

Apport de la scintigraphie dans le rein en fer à cheval : à propos d’un cas

We report a case of 6-year-old girl with Turner syndrome and recurrent urinary tract infections. Renal scintigraphy with Tc-99 m dimercaptosuccinic showed fusion of lower poles of the kidney parenchyma and no scar. Scintigraphy with Tc-99 m diethylene-triamine-penta-acetic acid (DTPA) with diuresis also showed fusion with lower pole and sign of right obstruction. This case report highlights the usefulness of functional imaging in the detection of congenital kidney, including the case of horseshoe kidney with fusion of the lower pole.     

The value of 99mTc-MIBI scan in the detection of malignancy potential of hypermetabolic thyroid incidentalomas of 18F-FDG PET/CT

Aim of the studyIncreasingly use of PET/CT leads to discovery of incidental findings. Hypermetabolic thyroid nodules are one of the unexpected lesions in PET/CT imaging with an increased risk of thyroid cancers. Our study aims to determine the malignant potential of incidentally detected 18F-FDG avid thyroid nodules by using Tc-99m MIBI imaging.Materials and methodsPET/CT scans were performed for nonthyroidal purposes and were evaluated for the presence of hypermetabolic thyroid nodules. Tc-99m MIBI scans and ultrasonography-guided fine needle aspiration biopsies were subsequently performed for all patients.ResultsPrimary thyroid malignancies were identified in 25% of patients with increased focal FDG uptake at definitive diagnosis. Among the patients with FDG avid thyroid nodules, Tc-99m MIBI scan showed true-positive results in all thyroid carcinomas (n:7) with a 36.3% (4/11) false-positivity rate. In three patients with indeterminate cytology results, Tc-99m MIBI scan findings were also negative. The sensitivity, specificity, positive predictive value of Tc-99m MIBI scan in predicting the malignancy of FDG-positive thyroid nodules were 100%, 77%, 63.6%, respectively.ConclusionThe implementation of ^99mTc-MIBI scan performed by dual phase and SPECT/CT modality might be a helpful cost-effective approach in addition to FNAB in patients with ¹⁸F-FDG-positive thyroid nodules and indeterminate cytology to improve the patients’ prognosis and reduce unnecessary thyroid operations with associated use of FNAB.     

Single-photon emission computed tomographic imaging of the early time course of therapy-induced cell death using technetium 99m tricarbonyl His-annexin A5 in a colorectal cancer xenograft model

As apoptosis occurs over an interval of time after administration of apoptosis-inducing therapy in tumors, the changes in technetium 99m ((99m)Tc)-tricarbonyl (CO)? His-annexin A5 (His-ann A5) accumulation over time were examined. Colo205-bearing mice were divided into six treatment groups: (1) control, (2) 5-fluorouracil (5-FU; 250 mg/kg), (3) irinotecan (100 mg/kg), (4) oxaliplatin (30 mg/kg), (5) bevacizumab (5 mg/kg), and (6) panitumumab (6 mg/kg). (99m)Tc-(CO)? His-ann A5 was injected 4, 8, 12, 24, and 48 hours posttreatment, and micro-single-photon emission computed tomography was performed. Immunostaining of caspase-3 (apoptosis), survivin (antiapoptosis), and LC3-II (autophagy marker) was also performed. Different dynamics of (99m)Tc-(CO)? His-ann A5 uptake were observed in this colorectal cancer xenograft model, in response to a single dose of three different chemotherapeutics (5-FU, irinotecan, and oxaliplatin). Bevacizumab-treated mice showed no increased uptake of the radiotracer, and a peak of (99m)Tc-(CO)? His-ann A5 uptake in panitumumab-treated mice was observed 24 hours posttreatment, as confirmed by caspase-3 immunostaining. For irinotecan-, oxaliplatin-, and bevacizumab-treated tumors, a significant correlation was established between the radiotracer uptake and caspase-3 immunostaining (r = .8, p < .05; r = .9, p < .001; r = .9, p < .001, respectively). For 5-FU- and panitumumab-treated mice, the correlation coefficients were r = .7 (p = .18) and r = .7 (p = .19), respectively. Optimal timing of annexin A5 imaging after the start of different treatments in the Colo205 model was determined.     

Treatment of tyramine-induced brain edema with anion transport inhibitor L-644,711

Tyramine induces coma in phenelzine-treated dogs. Development of coma in these animals is associated with brain edema, abnormal brain scans of Tc-99m-diethylene-triamine-penta-acetic acid (Tc-99m-DTPA), and elevated levels of CSF catecholamines. We found that the intravenous administration of 6-7 mg/kg of a single dose of L-644,711 given fifteen minutes after the oral administration of tyramine to phenelzine-pretreated animals followed by an infusion of normal saline containing 6-7 mg/kg of the drug given over a period of 2 hr caused reversal of brain injury. This was accompanied by full recovery within a period of 24 hr of all the animals tested. A follow-up study revealed that 24 hr after treatment with L-644,711 CSF levels of catecholamines and brain images of Tc-99m-DTPA were indistinguishable from normal controls. Animals that received no drug died from unresolved coma within 4 to 24 hr. Animals that had recovered due to therapy with L-644,711 were given 10-14 days rest followed by a repetition of the phenelzine and tyramine treatment but denied L-644,711 therapy. These animals also died of unresolved coma within 24 hr. This preliminary study suggest that the use of L-644,711 may constitute an important advance in treatment of brain edema of a wide range of neurological disorders.     

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

ObjectiveThe 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.MethodsA 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.ResultsThe 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.ConclusionThe 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. (Endocr Pract. 2014;20:310-319)     

Endothelial progenitor cells (EPCs) as gene carrier system for rat model of human glioma

Background

Due to their unique property to migrate to pathological lesions, stem cells are used as a delivery vehicle for therapeutic genes to tumors, especially for glioma. It is critically important to track the movement, localization, engraftment efficiency and functional capability or expression of transgenes of selected cell populations following transplantation. The purposes of this study were to investigate whether 1) intravenously administered, genetically transformed cord blood derived EPCs can carry human sodium iodide symporter (hNIS) to the sites of tumors in rat orthotopic model of human glioma and express transgene products, and 2) whether accumulation of these administered EPCs can be tracked by different in vivo imaging modalities.

Methods and Results

Collected EPCs were cultured and transduced to carry hNIS. Cellular viability, differential capacity and Tc-99m uptake were determined. Five to ten million EPCs were intravenously administered and Tc-99-SPECT images were acquired on day 8, to determine the accumulation of EPCs and expression of transgenes (increase activity of Tc-99m) in the tumors. Immunohistochemistry was performed to determine endothelial cell markers and hNIS positive cells in the tumors. Transduced EPCs were also magnetically labeled and accumulation of cells was confirmed by MRI and histochemistry. SPECT analysis showed increased activity of Tc-99m in the tumors that received transduced EPCs, indicative of the expression of transgene (hNIS). Activity of Tc-99m in the tumors was also dependent on the number of administered transduced EPCs. MRI showed the accumulation of magnetically labeled EPCs. Immunohistochemical analysis showed iron and hNIS positive and, human CD31 and vWF positive cells in the tumors.

Conclusion

EPC was able to carry and express hNIS in glioma following IV administration. SPECT detected migration of EPCs and expression of the hNIS gene. EPCs can be used as gene carrier/delivery system for glioma therapy as well as imaging probes.     

Sister chromatid exchanges in lymphocytes of nuclear medicine physicians

OBJECTIVE: The aim of this study was to assess whether occupational exposure to chronic, low doses of Iodine 131 (I-131) and Technetium 99m (Tc-99m) may lead to genotoxicity. Medical personnel occupied in nuclear medicine departments are occupationally exposed to low doses of I-131 and Tc-99m. The determination of the frequency of sister chromatid exchanges (SCEs) and of cells with a high frequency of SCEs (HFC) is considered to be a sensitive indicator for detecting genotoxic potential of mutagenic and carcinogenic agents. Therefore, we examined peripheral lymphocytes from nuclear medicine physicians for the presence of both SCE and HFC. METHODS: Sixteen exposed nuclear medicine physicians (non-smokers) were compared to 16 physicians (non-smokers) who had not been exposed to chemical or physical mutagens in their usual working environment at the same hospital. RESULTS: A statistically significant difference was found between SCE frequencies and HFC percentages measured in lymphocytes from the exposed and control groups. CONCLUSIONS: The present observation on the effect of chronic low doses of I-131 and Tc-99m indicates the possibility of genotoxic implications of this type of occupational exposure. Hence, the personnel who work in nuclear medicine departments should carefully apply the radiation protection procedures and should minimize, as low as possible, radiation exposure to avoid possible genotoxic effects.     

Lyophilization of TC-99m-Hynic Labeled Peg-Liposomes

Abstract

The development of long circulating liposomes represented a major step forward towards the use of radiolabeled liposomes in nuclear medicine. The long circulation property markedly improves their uptake and consequently visualization of sites of infection and inflammation. Previously, we have developed a rapid and convenient method to label polyethylene glycol (PEG)-lipo-somes with technetium-99m (Tc-99m). PEG-liposomes containing the technetium-chelator hydrazino nicotinamide (HYNIC) could be labeled with Tc-99m with high efficiency. We showed that these Tc-99m-HYNIC labeled PEG-liposomes have excellent in vivo imaging characteristics in several pre-clinical and clinical studies. However, an important limitation associated with the use of HYNIC-PEG-liposome formulation as radiopharmaceutical is that their labeling efficiency decreases markedly within 3 months. In this paper we present a lyophilization method for HYNIC-PEG-liposomes using sucrose as a lyopro-tectant. The long-term stability of these liposomes in terms of the particle size and labeling efficiency upon reconstitution were determined. Additionally, the in vivo behavior of reconstituted radiolabeled liposomes in a rat model of focal infection was studied at two time-points after preparation.

Increasing the duration of the dehydration step significantly reduced the mean particle size upon reconstitution. Increasing the storage temperature from -20^°C to +4^°C also improved the particle size distribution upon reconstitution. The labeling efficiency for both freeze-dried preparations remained high during the 1 year-storage period and was always higher than 86%, but decreased for the control liposomes. Eight months after preparation, these liposomes had a labeling efficiency as low as 6%, whereas both freeze-dried preparations could still be labeled with an efficiency of 90%. The in vivo studies showed that there was no major difference in the biodistribution of the radiolabeled liposomes between 3 and 30 weeks post-preparation in rats with an Staphylococcus aureus abscess, indicating an acceptable long-term shelf-life of both freeze-dried liposome preparations. Abscesses were visualized from 2 hours post injection onwards.

In conclusion, a freeze-drying method which improved the long term shelf-life of HYNIC-PEG-liposomes is presented. The in vivo behavior of Tc-99m-PEG-liposomes, reconstituted 30 weeks after preparation, was similar to the biodistribution obtained with the non-freeze-dried preparation. The splenic uptake of these liposomes was slightly increased.     

Renoprotective effect of Erdosteine in rats against gentamicin nephrotoxicity: a comparison of 99mTc-DMSA uptake with biochemical studies

Erdosteine is a mucolytic agent having antioxidant properties through its active metabolites in acute injuries induced by pharmacological drugs. This study was designed to investigate the renoprotective potential of Erdosteine against gentamicin (GM)-induced renal dysfunction by using Technetium-99 m dimercaptosuccinic acid (Tc-99 m DMSA) uptake and scintigraphy in rats. For this purpose, male Wistar rats were randomly allotted into one of the four experimental groups: Control, Erdosteine, GM, and GM + Erdosteine groups. GM and GM + Erdosteine groups received 100 mg/kg GM intramuscularly for 6 days. In addition, Erdosteine and GM + Erdosteine groups received 50 mg/kg Erdosteine orally for 6 days. Renal function tests were assessed by serum blood urea nitrogen (BUN), creatinine levels, as well as scintigraphic and tissue radioactivity measurements with Tc-99 m DMSA. Renal oxidative damage was determined by renal malondialdehyde (MDA) levels, by antioxidant enzyme activities; superoxide dismutase (SOD) and catalase (CAT) and activities of oxidant enzymes; xanthine oxidase (XO) and myeloperoxidase (MPO). GM administration resulted in marked renal lipid peroxidation, increased XO and MPO activities and decreased antioxidant enzyme activities. GM + Erdosteine group significantly had lower MDA levels, higher SOD and CAT activities and lower XO and MPO activities, when compared to GM. Also GM + Erdosteine had lower levels of serum BUN, creatinine and higher renal tissue Tc-99 m DMSA uptake and radioactivity with respect to GM. In conclusion, our results supported a protective role of Erdosteine in nephrotoxicity associated with GM treatment.     

Nitroimidazoles and hypoxia imaging: synthesis of three technetium-99m complexes bearing a nitroimidazole group: biological results

Several Tc-99m complexes were synthesized, substituted with a nitroimidazole group, in order to visualize hypoxic tissues. The complexes were tested on rats (isolated hearts) and showed no significant uptake under hypoxic conditions.     

The renal parenchyma evaluation: MAG3 vs. DMSA

Scintigraphy with Tc-99m dimercaptosuccinic acid (DMSA) is considered a reference method for assessment of parenchymal lesions and estimation of differential kidney function. The aim of study was to evaluate Tc-99m mercaptoacetyltriglycine (MAG3) dynamic renal scintigraphy for the same purpose. 188 patients, submitted to both studies within three months, were divided in two groups. In the first, 83 DMSA images were compared to parenchymal phase of MAG3 scintigraphy. Kidney morphology was independently evaluated by four observers. In the second group (N = 105), differential function was calculated in MAG3 and DMSA studies and the respective results were compared. Findings corresponded completely in 85% of patients. There were no statistically significant differences between calculated differential function on DMSA and MAG3 images. The results showed that most of parenchymal lesions detected on DMSA scans can be identified on MAG3 parenchymal scans. Both studies can be equally used for the calculation of differential kidney function.     

AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study

Background  

Despite enormous progress in gene therapy for breast cancer, an optimal systemic vehicle for delivering gene products to the target tissue is still lacking. The purpose of this study was to determine whether AC133+ progenitor cells (APC) can be used as both gene delivery vehicles and cellular probes for magnetic resonance imaging (MRI). In this study, we used superparamagentic iron oxide (SPIO)-labeled APCs to carry the human sodium iodide symporter (hNIS) gene to the sites of implanted breast cancer in mouse model. In vivo real time tracking of these cells was performed by MRI and expression of hNIS was determined by Tc-99m pertechnetate (Tc-99m) scan.     

Bone Marrow Uptake in Parathyroid Scintigraphy is A Consequence of Extremely High Parathyroid Hormone Levels

ObjectiveWe retrospectively evaluated patients with end-stage renal disease (ESRD) who were referred to our department for parathyroid scintigraphy. The aim of this study was to investigate the causes of bone marrow uptake observed on parathyroid scintigraphy.MethodsWe included 18 ESRD patients (10 F, 8 M; mean, 52 ± 13 years old; range, 45-59) in the study. The disease duration of the patients was mean 7.7 ± 4.7 years. The patients’ mean plasma calcium and parathormone (PTH) levels were 9.7 ± 1.4 mg/dL and 1,553.3 ± 691.7 pg/mL, respectively. Dual-phase technetium-99m 2-methoxyisobutyl-isonitrile (Tc-99m MIBI) parathyroid imaging and, if necessary, additional Tc-99m pertechnetate scintigraphy were performed. Quantification of the planar early phase parathyroid images was performed for various regions (sternum, humerus, ribs) with the same size rectangular region of interest (ROI, 176 × 176 pixels). Average counts were compared with paired samples Student’s t tests, and P <.05 was considered statistically significant.ResultsTc-99m MIBI parathyroid imaging revealed parathyroid hyperplasia, adenoma, and ectopic adenoma in 7, 3, and 2 patients, respectively. The other 7 patients had normal scintigraphy results with regard to parathyroid pathologies. Bone marrow uptake in the sternum, ribs, and humerus was observed in 6 patients. The difference between the average quantitative value obtained from the ROIs drawn on the sternum and humerus was also statistically significant compared to patients without bone marrow uptake (P<.05). All 6 patients’ exhibited extremely high PTH levels (>2,000 pg/mL; mean, 2,413.7 ± 150 pg/mL) compared to the other 12 patients (mean, 1,342.8 ± 249 pg/mL).ConclusionOur results show that bone marrow uptake on parathyroid scintigraphy is a consequence of extremely high PTH levels in ESRD patients; no further analysis is required. (Endocr Pract. 2013;19:202-205)     

Imaging of chemiluminescent reactions in mesoscale silicon-glass microstructures

Chemiluminescent reactions in mesoscale analytical structures (chips) containing micrometer-sized interconnecting channels and chambers (pL-nL total volume) were imaged. The chips were fabricated by bonding Pyrex glass to etched pieces of silicon using a high-temperature diffusive bonding technique. In initial experiments light emission from an enhanced chemiluminescent horseradish peroxidase reaction and from a peroxyoxalate reaction contained in straight channels (300 μm wide × 20μ deep; volume 70.2 nL) and open chambers (812 μm wide, 400 μm deep, 5.2 mm long) linked by channels (100μm wide, 20 μm deep) to an exit and entry port were studied using a specially modified microplate holder and an Amerlite microplate luminometer. Light emission from more complex structures (two chambers interconnected by a branching channel 100 μm wide, 20 μm deep) filled with a solution containing alkaline phosphatase, Emerald, and CSPD^TM was imaged using a Photometrics Star 1 CCD camera. Detailed investigation of the detection and spatial resolution of the signal was performed on a Berthold Luminograph LB 980 using both the enhanced chemiluminescent horseradish peroxidase reaction and a peroxyoxalate reaction. We successfully resolved light emission from silicon structures with dimensions 100 μm wide and 20 μm deep. These simple silicon structures served as models for more complex designs that will be used for simultaneous multi-analyte assays in which an imaging system resolves and quantitates light emission from different locations on a silicon-glass analytical device.     

Evaluation of the cytotoxic and mutagenic potentiality of technetium-99m in Escherichi coli.

Since technetium-99m (99mTc) was introduced in medical research it has become one of the most employed radionuclides in nuclear medicine. 99mTc is ideal for routine use on the labeling of different radiopharmaceuticals due to its favorable characteristics. However, some biological effects have been described. These effects may be related to internal conversion electron and/or Auger electron emissions from 99mTc decay that present high linear energy transfer and can generate reactive oxygen species (ROS) in the medium. We evaluated in Escherichia coli K12S and Salmonella typhimurium TA102, both proficient in DNA repair, contribution of those decay emissions on the cytotoxicity induced by 99mTc, both either by generating lesions on DNA or by inducing alterations at membrane. We also studied the genotoxic and/or mutagenic potentiality of 99mTc, in Salmonella typhimurium, using the Ames test. The results showed that: i/ 99mTc is cytotoxic to the Escherichia coli K12S strains; ii/ this effect is related to the electrons (Auger and internal conversion) emissions, and iii/ the 99mTc is not mutagenic and/or genotoxic, when measured by Ames test.