Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. IV. Interaction of 99mTc-DMS and 99Tc-DMS complexes with blood serum proteins

As a crucial step towards understanding the mechanism of localisation of radiopharmaceuticals in specific target organs, the interaction of the radiopharmaceuticals 99mTc-DMS and 99Tc-DMS with blood serum proteins was studied. The interaction of 99mTc-DMS radiopharmaceutical was examined from two aspects: total protein binding as well as specificity of binding to certain classes of proteins. After in vitro labelling of human sera with 99mTc-DMS, the following values of bound radioactivity to total serum proteins were determined: 65% +/- 3.2% by gel-filtration chromatography; 72% +/- 4.6% by dialysis; while on the basis of precipitation by perchloric and trichloroacetic acid 72.7% +/- 6.8% and 71% +/- 2.3%, respectively. Distribution of 99mTc-DMS or 99Tc-DMS among serum proteins was analysed by agarose gel electrophoresis of the sera at pH 8.6 after in vivo and in vitro labelling of human sera with 99m-Tc-DMS, while the same analysis was performed with 99Tc-DMS complex after in vitro labelling of human and rat sera as well as after in vivo application to the rats. The results obtained demonstrate that carrier serum proteins investigated by agarose gel electrophoresis were in the migration zone of alpha 2-, alpha 1- and beta 1-globulins, whereas the radioactivity found in the serum albumin zone was negligible. Interaction of both Tc-DMS complexes with proteins was very similar, and this conclusion was in good correlation with our previously obtained results in investigations concerning the biochemical behaviour of these complexes.     

Effect of mitochondrial viability and metabolism on technetium-99m-sestamibi myocardial retention

This study investigated the mechanism of myocardial retention of technetium-99m-sestamibi.^99mTc-sestamibi was injected intravenously into guinea pigs, and the myocardium was homogenized and fractionated by differential centrifugation. More than 90% of myocardial^99mTc-sestamibi was localized within the mitochondrial fraction. Calcium was found to release^99mTc-sestamibi from the mitochondrial fraction, with an IC₅₀ of 2.54±0.98 mM. This effect was potentiated by NaCl, and inhibited by the mitochondrial calcium channel blocker ruthenium red. In vitro uptake of^99mTc-sestamibi was found to increase from 10.5% ± 3.0% to 61.2% ± 0.2% with the addition of 10 mM succinate, indicating that respiration is involved. Since irreversible ischemia results in cellular and mitochondrial calcium overload and loss of mitochondrial metabolic function,^99mTc-sestamibi should not be retained in necrotic or irreversibly ischemic myocardium, and could potentially act as a sensitive indicator of myocardial cell viability.     

Labelling of leucocytes with colloidal tech netium-99m-SnF2: an investigation of the labelling process by autoradiography

Autoradiography of smears and frozen sections of labelled cell suspensions was used to study the distribution of radioactivity in and among blood cells labelled in either whole blood or leucocyte-rich plasma (LRP) with technetium-99m-SnF₂ colloid. The tracer proved selective for neutrophils: the labelling probability (relative to that for erythrocytes) for each cell type in LRP (mean of five samples) was: neutrophils, 9.4; lymphocytes, 3.7; monocytes, 3.0; eosinophils 1.4; erythrocytes, 1.0. When labelling was carried out in whole blood (five samples), 74.5%±8.3% of the cell-bound radioactivity was bound to erythrocytes, 13.6%±6.5% to neutrophils, and 11.9%±2.1% to lymphocytes, whereas in LRP (in which the leucocytes were only slightly out-numbered by erythrocytes), 76.5%±14.9% of radioactivity was neutrophil bound. Labelled cells in smear autoradiographs exhibited two distinct silver grain patterns, diffuse, consistent with an intracellular radioactive particle (in neutrophils), and focal, consistent with a cell surface-adhering particle in direct contact with the emulsion (in other leucocyte types and erythrocytes). The phagocytic inhibitor cytochalasin B neither reduced the proportion of labelled neutrophils nor altered the labelling pattern. Neutrophils were able to scavenge radioactivity from the surface of erythrocytes. It is concluded that neutrophils bind^99mTc-SnF₂ intracellularly by phagocytosis, with high affinity; other cells become labelled at the cell surface reversibly and with lower affinity. This selectivity is high enough to permit predominantly leucocyte labelling in LRP but not in whole blood.     

99mTc-labelling of leucocytes with 99mTc-DPO: a complex developed for myocardial imaging

The lipophilic ^99mTc-DPO complex, developed as a myocardial imaging radiopharmaceutical, was used to label leucocytes. After an incubation of 0.1 ml ^99mTc-DPO (8 g DMPE*2HCl) with mixed leucocytes in plasma, the labelling efficiency was over 70%. During incubation in 5 ml plasma, a loss of activity was found between 20% (1 h) and 35% (3 h) caused by elution. Disturbances of cell viability could not be found with the help of the chemiluminescence test. The in vivo recovery was determined in three dogs and was 45%–50% (0.5 h), 30%–36% (1 h), and 18%–24% (3 h). Autologous ^99mTc-DPO-leucocytes were used on seven patients with suspected osteomyelitis, there were four true negative and three true positive results. The target/nontarget ratio determined by ROI in the positive cases was 1.8 to 2.5 at 3 h after injection.     

Evaluation of 99mTc-dextran as a lymphoscintigraphic agent in rabbits

Dextran (clinical grade, average mol. wt. 82,200) was labelled with ^99mTc and the labelling efficiency was checked by paper and thin-layer chromatography and electrophoresis. The amount of free ^99mTcO ₄ ^- was always less than 1%. The radiopharmaceutical was injected ID into the web space in hind legs of ten rabbits (200–600 Ci/0.05 ml). Scintigrams were taken at 10-min intervals up to 3 h in three rabbits. The injection site and the hind legs were massaged after injection in the other seven rabbits and scintigrams were taken at 10-min intervals up to 2 h. Blood samples were obtained at 5, 15, 30, 90 and 120 min in both groups. In addition a 180-min sample, was also taken in the first group. At the end of the study the rabbits were killed and the popliteal lymph nodes and the organs were removed to be weighed, and counted. Our results indicated a high concentration of radioactivity in the popliteal lymph nodes and massage at the injection site increased the average uptake of the popliteal lymph node from 1.12%±0.77% to 4.28%±1.57% at 3 and 2 h, respectively (P<0.001). In scintigrams the lymph channels and the nodes were very well visualised. The blood radioactivity levels were too low to present a background problem. With massage 30% of the injected dose was removed from the injection site in 2 h. We have shown that ^99mTc-dextran is a good radiopharmaceutical for the visualisation of the lymph system and deserves further experimental and clinical studies.     

Stabilisation of high-activity99mTc-d,I-HMPAO preparations with cobalt chloride and their biological behaviour

It has been reported that the stability of a 1.11-GBq (30 mCi) technetium-99md,l-hexamethylpropylene amine oxime (HMPAO) preparation can be improved to up to 5 h by the addition of 200 g CoCl₂·6H₂O within 2 min after reconstitution. However, it is not clear whether this method is also efficient for high-activity preparations (5.55 GBq) and whether this modified^99mTc-d,l-HMPAO has the same biological properties and can safely be used. We have now studied CoCl₂-stabilised^99mTc-d,l-HMPAO preparations containing different amounts of in-house HMPAO ligand and SnCl₂ and reconstituted with activities from 1.11 GBq to 5.55 GBq^99mTc. The characteristics of the generator eluates were also divergent, ranging from fresh eluates from a generator eluted less than 2 h previously to 4-h-old eluates from a generator not eluted during the preceding 72 h. Preparations containing up to 5.55 GBq^99mTc and as low as 2 g SnCl₂·2H₂O can be efficiently stabilised for at least 6 h by the addition of CoCl₂ shortly after reconstitution. Interestingly, it was found that the stabilisation method is not efficient if the cobalt ions are added prior to reconstitution of the preparation. This implies that the cobalt chloride cannot be incorporated in the labelling kit. Also, preparations with amounts of the ligand lower or higher than 0.5 mg formed the^99mTc-d,l-HMPAO complex with low radiochemical yield or showed rapid degradation. Therefore, combination of a subdivision and storage of Ceretec kits in fractions (as reported in the literature) is contra-indicated with this CoCl₂ stabilisation method. CoCl₂-stabilised Ceretec kits reconstituted with 5550 MBq^99m-TcO₄ ^- and used 4–5 h after preparation retain the diagnostic usefulness of the fresh 1110-MBq preparation with regard to leucocyte labelling and brain imaging. Although baboon brain uptake of the stabilised preparation was 6%–9% lower, this small difference could not be distinguished in the tomographic images. The data obtained with both inhouse preparedd,l-HMPAO and Ceretec kits suggest that the eluate restrictions recommended by the Ceretec manufacturer can be neglected if the preparation is stabilised with Co²⁺ ions. Studies with⁵⁷Co-spiked CoCl₂ added tod,l-HMPAO preparations demonstrated that the Co²⁺ ions clearly interact with thed,l-HMPAO ligand, probably to form one or more complexes. From biodistribution studies in mice it became evident that the toxicological profile of the Co²⁺ ions in the presence ofd,l-HMPAO should be more favourable than that of cobaltous ions. For these reasons, it seems justifiable that CoCl₂-stabilised^99mTc-d,l-HMPAO preparations should undergo rigorous studies to elucidate their clinical usefulness and pharmacological safety.     

Measurements of the rubidium isotopic activities and the elution parameters of 81mKr generators using a standardized 114mIn source

A method is described for measuring a number of parameters associated with an inorganic ion-exchange krypton generator. These are the activities of rubidium isotopes in inorganic ion-exchange krypton generators, the ^81mKr extraction rate, the ^81mKr activity delivered to patients during ventilation studies, the elution efficiency, and the radionuclide purity of the eluted gas. The method is based on the calibration of detectors, Ge(Li) and NaI(Tl), with a standardized ^114mIn source at matching photon energies. The average activities present in our generators at the end of bombardment (EOB) were 14.6±3.8 mCi (⁸¹Rb), 6.2±1.6 mCi (^82mRb) and 53±9.4 Ci (⁸³Rb). The ^81mKr extraction rate 2 h post-EOB was 10.2±2.3 mCi/min at an air flowrate of 1 l/min. The ^81mKr activity delivered to patients during a ventilation study was 91±16 mCi. The elution efficiency of the generators averaged 50%±7% at an air flowrate of 1 l/min. The eluted gas contained Rb radioisotopic impurities in trace quantities of approximately 0.06 Ci/l.     

Studies of 99mTc-acylplasmins as agents for thrombus detection

It has been proposed that acylation at the active site of plasmin is able to prevent its reaction with 2-antiplasmin without affecting the fibrin affinity of the enzyme. To investigate the possibility that ^99mTc-labelled acylplasmins are improved thrombus-detecting agents, six acylating agents were synthesised and their reaction with plasmin and the labelling of the products with ^99mTc studies. Uptake of ^99mTc-acylplasmins in an in vitro thrombus model was complicated by precipitation processes, which may in part account for the rapid blood clearance in rabbits and high liver uptake in mice injected with the compounds. Quantitative measurements using an in vivo rabbit thrombus model demonstrated that guanidinobenzoyl-plasmin exhibited nearly a threefold increase in thrombus uptake compared with non-acylated ^99mTc-plasmin. The observed uptake is less than that obtained with ¹²⁵I-fibrinogen at clinically useful time intervals post-injection but represents a significant advantage over the use of ^99mTc-plasmin.     

Pharmacokinetics and biodistribution of samarium-153-labelled OC125 antibody coupled to CITCDTPA in a xenograft model of ovarian cancer

The use of samarium-153 in the context of radioimmunotherapy of cancers has been limited by the instability of antibody labelling, which produces high uptake concentrations in liver and bone. This study compares the pharmacokinetics and biodistribution of¹⁵³Sm-labelled OC125 monoclonal antibody, in whole or F(ab)₂ fragment form and with diethylene triamine penta-acetic acid (DTPA) or 6-p-isothiocyanatobenzyl diethylene triamine penta-acetic acid (CITCDTPA) coupling, in nude mice grafted subcutaneously with an ovarian adenocarcinoma line (SHIN-3) expressing CA125 antigen. The specific activity of the immunoconjugates was 18.5–55.5 MBq/mg, and their immunoreactivity exceeded 65%. With¹⁵³Sm-DTPA-OC125F(ab)₂, the stability study in serum indicated that 50% of the metal remained bound to the antibody. The pharmacokinetic study showed a retention half-life of 25.1 h and blood clearance of 0.72 ml/h. The biodistribution study indicated tumour uptake of 4.53%±9% of injected activity per gram (%ID/g) at 24 h and tumour-to-liver and tumour-to-bone ratios of 0.23±0.02 and 1.54±0.49 respectively at 24 h. With¹⁵³Sm-CITCDTPA-OC125F(ab)₂, serum stability was greater (87% of the metal remaining bound to the antibody), retention half-life was 22.25 h and blood clearance was 2.23 ml/h. Tumour was better targeted (8.30%±3.56%ID/g at 24 h), and tumour-to-liver and tumour-to-bone ratios were 1.17±0.36 and 7.08±3.09 respectively at 24 h. However, renal retention remained elevated (29.76%±9.41%ID/g at 24 h). With intact IgG, renal uptake decreased (1.41%±0.49%ID/g at 24 h), but tumour uptake was lower than with fragments (1.46%±0.58%ID/g at 24 h). Liver uptake was higher (tumour-to-liver ratio 0.10±0.05), and blood clearance was slower. The stability and distribution of¹⁵³Sm-CITCDTPA were more favourable than those of¹⁵³Sm-DTPA for application in radioimmunotherapy. Quantitative analysis performed using digitized images obtained by conventional autoradiography and the imaging plate system indicated that the latter system is suitable for bio-distribution studies of immunoconjugates.     

Radiochemistry and biostability of autologous leucocytes labelled with 99mTc-stannous colloid in whole blood

Autologous leucocytes were labelled in whole blood by phagocytic uptake of ^99mTc-stannous colloid. This colloid has a mean particle size of 1.5 m and labels leucocytes with 81% efficiency. Individual cell uptakes were: granulocytes 42%, monocytes 39%. Isotonic sodium citrate added after the labelling procedure did solubilise excess colloid but was not necessary for adequate removal of excess colloid. Labelled leucocytes were shown in vitro to be viable and maintain normal bactericidal and chemotactic capacity. Biodistribution, clearance rates and dosimetry are presented. These results indicate that autologous leucocytes can be efficiently labelled with ^99mTc-stannous colloid with good residual cell function.     

Brain perfusion scintigraphy with99mTc-HMPAO or99mTc-ECD and123I-β-CIT single-photon emission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease

Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) or^99mTc-ethyl cysteinate dimer (^99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2-carboxymethoxy-3-[4-iodophenyl]tropane (¹²³I--CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of^99mTc-HMPAO or^99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of¹²³I--CIT binding was 2.5±0.4, with an increase to 5.5±1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of¹²³I--CIT binding was significantly reduced to 1.7±0.3, with a modest increase to 2.1±0.4 18 h after tracer injection (P<0.05, Scheffe test, ANOVA). These results suggest that^99mTc-HMPAO or^99mTc-ECD and¹²³I--CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.     

Results of brain scanning with different radioisotopes (99mTc-PP, 99mTc-DTPA, 67Ga citrate)

Summary A comparison of the results obtained by ^99mTc-DTPA, ^99mTc-PP and ⁶⁷Ga-citrate scanning in ten meningioma patients is reported. The association of conventional brain scanning, bone scanning and tumor-positive scanning makes it possible to identify the primary tumor, its real extent, the perifocal damage and the contiguous bone damage.

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Ergebnisse der Hirn-Szintigraphie mit verschiedenen Substanzen

Zusammenfassung Die Verfasser vergleichen die abgegebenen Ergebnisse von ^99mTc-DTPA, ^99mTc-PP und ⁶⁷Ga-citrate bei 10 Patienten, von Meningiom befallen. Die Vereinigung der üblichen Hirn-Szintigraphie, der Knochen-Szintigraphie und der positiven Tumor-Szintigraphie erlauben die Identifizierung des ursprünglichen Tumors, seiner wirklichen Ausdehnung, des perifokalen Schadens und der angrenzenden Knochen-Veränderung.

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Etude comparative de la scintigraphie cérébrale avec differenis radio-elements (99^mTc-PP. 99^mTc-DTPA, 67 Ga citrate)Première partie: Etude des méningiomes

Résumé Les auteurs comparent les résultats de la scintigraphie cérébrale avec ^99mTc-DTPA, ^99mTc-PP et ⁶⁷Ga-citrate dans 10 cas de meningiome. L'association de la scintigraphie cérébrale conventionnelle, de la scintigraphie osseuse et de la scintigraphie néoplastique positive consent d'individualiser le foyer néoplastique, l'extension, le damage periphocale et l'altération osseuse concomitante.

     

Experimental biodistribution studies of 99mTc-recombinant human serum albumin (rHSA): a new generation of radiopharmaceutical

Recombinant human serum albumin (rHSA) produced by cultured fermentation has been prepared in the form of microcapsules nominally 3–5 m in diameter and radiolabelled with technetium-99m following reduction with stannous chloride. Radiochemical purity was assessed by chromatography on instant thin-layer chromatography and found to be greater than 90%. No evidence of aggregation was seen by microscopic examination. Imaging biodistribution studies in New Zealand white rabbits demonstrated targeting to the liver or lung, respectively, depending upon the size and surfactant properties of the microcapsules. This communication is the first to show scintigraphic studies using ^99m-Tc-labelled rHSA with the potential for lung, liver and cardiovascular imaging and demonstrates that recombinant DNA technology offers an important new source of materials suitable for use as radiopharmaceuticals without the need for pooled human blood products.     

A chemical method for the labeling of fibrinogen with 99mTc

A new method allowing the labelling of fibrinogen with ^99mTcO ₄ ^- is described. The ^99mTcO ₄ ^- is reduced by stannous chloride in an alkaline medium. After 1 h incubation with fibrinogen, the pH was brought down to 7.1. The study of (1) the pH of the solution, (2) the quantity of the reducer, and (3) the time of incubation allowed us to specify optimal conditions for labeling. The labeling yield varied from 91.68%±6.05% to 95.18%±2.13% according to the method of control used: the precipitation of fibrinogen by (NH₄)₂SO₄ 25% or thin-layer chromatography with methylethylketone as solvent. Clottable radioactivity averaged 72%±4.43%. Column chromatography separated the tracer into two radioactive peaks. The first peak corresponded to the fibrinogen and carried 73.36%±5.8% of the total radioactivity. The total recovered radioactivity amounted to 89.86%±8.07%. Spectroscopic clottability was 88.23%±2.42%.The in vivo stability of the labeling and the molecule was followed for 24 h after intravenous injection. If the radioactivity measured in the 5 min sample was considered to equal 100%, the 24 h sample averaged 32.71%±3.25%, of which 85.68%±2.92% was recovered in the clot. In conclusion, this method enabled us to obtain a stable tracer that we used for routine investigations in man.     

The effect of parathyroid hormone on technetium-99m pyrophosphate distribution in rats

Sprague-Dawley rats were treated with varying quantities of parathyroid hormone for 1–3 days, then sacrificed at periods ranging from 1–6h after administration of ^99mTc-pyrophosphate. Very little increase in bone accumulation of tracer occurred with this treatment. A small, but obvious decrease occurred in the blood levels of ^99mTc-pyrophosphate and a smaller and less consistent decrease was affected in the muscle levels of the radiopharmaceutical. The overall result was an improvement in the bone/blood and bone/muscle ratios. It is suggested that the basis of the supernormal bone scan of hyperparathyroidism is achieved by this mechanism and that the increased bone uptake of other ions in response to parathyroid hormone is not shared by ^99mTc-pyrophosphate.Supported by the Veterans Administration     

Bromine-82 contamination in fission product 99mTc-generator eluate

Following receipt of fission product ^99mTc-generators, results of radionuclide purity analysis, performed within 30 min after the first elution, demonstrated detectable levels of a contaminate radionuclide not previously reported. Gamma spectroscopy and half-life determinations confirmed the presence of ⁸²Br. Bromine-82 activity, in eluates from the first elution of 30 generators, received weekly during a 7-month period, ranged from 0.22 Ci (8.235 kBq) to 0.67 Ci (24.68 kBq) per eluate. The ratio of ⁹⁹Mo to ^99mTc ranged from 0.13 nCi to 0.39 nCi per mCi ^99mTc. The presence of ⁸²Br in ^99mTc-generator eluate resulted in falsely elevated ⁹⁹Mo assay determinations using whole vial ⁹⁹Mo assay procedures. For every 0.1 Ci ⁸²Br present in ^99mTc eluate the ⁹⁹Mo assay results were elevated by 1 Ci. Gamma spectroscopy of eluates from additional elutions of these generators failed to detect the presence of ⁸²Br demonstrating the displacement of monovalent bromine anions from the alumina column during the first elution.     

A simple method of evaluating the penetrability of Spitz-Holter drains with the aid of radioisotopes

A simple, reliable, and innocuous method is deseribed for evaluating the penetrability of cerebrospinal shunts with the use of ^99mTc O₄. After introducing 25 Ci of ^99mTc O₄ in a volume of about 0.2 ml into Rickham's reservoir, series scintigrams in the lateral or AP direction are made with the aid of a Nuclear Chicago Pho Gamma HP Scintillation Camera.The results are in satisfactory agreement with the surgical findings. No complications have so far been observed.     

Detection of coronary artery disease by dynamic planar and single photon emission tomographic imaging with technetium-99m teboroxime

To test the clinical significance of technetium-99m teboroxime regional myocardial clearance in the detection of coronary artery disease, 25 patients underwent dynamic planar or single-photon emission tomographic (SPET) myocardial imaging with ^99mTc-teboroxime after exercise and again 2 h later at rest. All patients underwent both thallium-201 exercise and redistribution SPET and coronary arteriography. The early phases of exercise ^99mTc-teboroxime myocardial clearance determined by dynamic planar imaging showed a significant difference between normal and post-stenotic myocardial regions (clearance rate constant k: 0.047±0.005 min' versus 0.034±0.003 min^–1, P <0.001). Reflecting this differential clearance between myocardial regions, an early redistribution-like phenomenon was observed in a significant number of myocaridal segments by comparing serially acquired post-exercise ^99mTc-teboroxime SPET images. These results indicated that the analysis of ^99mTc-teboroxime myocardial clearance was of potential use in the detection of coronary artery disease, yielding additional information to that provided by the tracer distribution analysis. Although the early redistribution-like phenomenon of ^99mTc-teboroxime could be the source of underestimation of ischaemia if acquisition of the initial post-exercise image were delayed, it could also prove useful in the early differentiation of ischaemia from scar because when the phenomenon was observed in delayed post-exercise images, the rest study could be omitted under some circumstances.     

99mTc-sestamibi thyroid uptake in euthyroid individuals and in patients with autoimmune thyroid disease

Purpose We investigated the biokinetics of ^99mTc-sestamibi in the thyroid of euthyroid volunteers (EVs) and in patients with autoimmune thyroid diseases and determined the best time interval between ^99mTc-sestamibi injection and calculation of uptake.Methods Forty EVs, 30 patients with Graves disease (GD), 15 patients with atrophic Hashimotos thyroiditis (AHT) and 15 patients with hypertrophic Hashimotos thyroiditis (HHT) underwent ^99mTc-sestamibi thyroid scintigraphy. Dynamic images were acquired for 20 min, and static images were obtained 20 min, 60 min and 120 min post injection. Five-, 20-, 60- and 120-min uptake, time to maximal uptake (T_max) and T_1/2 of tracer clearance were calculated. Thyroid hormones and antibodies were measured. ^99mTc-pertechnetate uptake was investigated in GD patients.Results T_max was approximately 5 min in all four groups. The mean T_1/2 value for EVs was similar to the GD value and lower than the HHT and AHT values. The mean (±SD) 5-min uptake was 0.13% (±0.05%) for EVs. The 5-min uptake in GD was higher than that in EVs(P<0.001) and correlated with free thyroxine (r=0.54) and with ^99mTc-pertechnetate uptake (r=0.68). Uptake in HHT was higher than that in AHT (P=0.0003) and EVs (P=0.002). Uptake in AHT was lower than uptake in EVs (P=0.0001).Conclusion Five minutes is the optimal time interval between ^99mTc-sestamibi injection and calculation of thyroid uptake. Five-minute uptake differentiates euthyroid individuals from GD patients. There is a high correlation between ^99mTc-sestamibi and ^99mTc-pertechnetate uptake in GD. The reduced ^99mTc-sestamibi uptake in AHT patients is probably due to glandular destruction and fibrosis. Inflammatory infiltrate and high mitochondrial density in thyrocytes possibly explain the increased uptake in GD and HHT.     

Measurement of the secretion of technetium-99m hexamethylpropylene amine oxime into breast milk

There are no published data for the activity of technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) found 1in breast milk. The amount of radioactivity in breast milk following the administration of 500 MBq^99mTc-HMPAO for a brain perfusion study has been measured. The effective dose to the infant was calculated to be 0.26 mSv, so necessitating no interruption of breast feeding. Unbound^99mTc is readily secreted into breast milk and the effective dose will remain less than 1 mSv if the^99mTc-HMPAO labelling effici ency is 99% for the worse reported case, and could remain <1 mSv for the mean reported case for^99mTc-HMPAO labelling efficiencies down to 94%.