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A method for stabilising technetium-99m exametazime prepared from a commercial kit.

Technetium-99m exametazime (99mTc-d,l-HMPAO), prepared by the reconstitution of the Ceretec kit, is widely used in the investigation of regional cerebral blood flow. The radiochemical purity specification of not less than 80% lipophilic complex requires that the kit is used within 30 min of reconstitution. In certain circumstances this imposes restrictions on its clinical availability. A number of approaches to extending the 30-min shelf life have been proposed and these are discussed. A method of stabilising the kit by the addition of 200 micrograms cobalt chloride hexahydrate (CoCl2 x 6H2O) in 2 ml of water is described. The addition of this solution can extend the shelf life of the reconstituted kit to at least 5 h post reconstitution.

Drug Stability↗

Quantification of technetium-99m hexamethylpropylene amine oxime brain uptake in routine clinical practice using calibrated point sources as an external standard: phantom and human studies.

Quantitative methods for calculation of regional cerebral blood flow with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) have been proposed. These methods are very labour intensive and therefore are not useful in routine clinical practice. We describe a simple alternative method, using calibrated point sources as a scaling factor, whereby the tomographic slices are displayed as regional 99mTc-HMPAO brain uptake per cm3 brain tissue in 10(-6) of the injected lipophilic dose. The method was validated on Jaszczak and Hoffman phantoms using a three-detector system with HR parallel and HR fan-beam collimators. Under the optimal conditions described in this paper, the measured to real activity ratio was 1.00 (SD = 0.06). The reproducibility of the cerebellar uptake in a group of ten normal volunteers and five patients was studied. Intra-individually a mean deviation of 12.6% was observed for the total group. For those persons with a heart rate difference of less than 5 units between the two studies, a mean deviation of 7.2% was obtained. Quantitative 99mTc-HMPAO brain uptake images can be useful for longitudinal studies, especially for follow-up, activation and pharmacological studies.

Adult↗

Radioimmunoscintigraphy with technetium-99m labelled monoclonal antibody, 1A3, in colorectal cancer.

This study of radioimmunoscintigraphy (RIS) was primarily undertaken to determine how the imaging results related to surgical findings. Technetium-99m radiolabelled 1A3, a monoclonal antibody against a columnar cell surface antigen, was used. No adverse effects or thyroid uptake was observed in 127 studies. The 85 primary colorectal cancers were all image positive. In the assessment of recurrent tumour in the abdomen or pelvis, the accuracy was 33/35 (94%), including true-positive findings in some whose serum carcinoembryonic antigen was normal. There was a positive predictive value for abdominal or pelvic recurrence of 92% and a negative predictive value of 100%, at a prevalence of 66%. In those patients whose liver was able to be evaluated, the accuracy was 72/79 (91%). There was a positive predictive value for liver metastases of 88% and a negative predictive value of 93%, at a prevalence of 32%. The simple procedure for labelling antibody with 99mTc and its ready availability allow a completed report to be given within 24 h of the request.

Adult↗

Hypertension in paediatrics: can pre- and post-captopril technetium-99m dimercaptosuccinic acid renal scans exclude renovascular disease?

In children over 1 year of age, renal disease is the commonest cause of hypertension. Arteriography is considered the reference method to establish the diagnosis of renovascular disease; however, it is an invasive technique with a high radiation burden for children. This was a retrospective study of pre- and post-capto-technetium-99m dimercaptosuccinic acid (DMSA) imaging compared with arteriography in 18 children between the ages of 3 and 17 years. Alone, the 99mTc-DMSA scan is a sensitive indicator of renal parenchymal disease, although non-specific in suggesting the pathology. The combination of pre- and post-captopril studies may increase the sensitivity and specificity in the diagnosis of renovascular disease in the presence of hypertension. This work suggests that a screening investigation with a low radiation burden can be carried out at most institutions; if the investigation is positive, there will be a high index of suspicion that renovascular disease is the cause of the hypertension.

Adolescent↗

Localization of parathyroid enlargement: experience with technetium-99m methoxyisobutylisonitrile and thallium-201 scintigraphy, ultrasonography and computed tomography.

Technetium-99m methoxyisobutylisonitrile (MIBI), like thallium-201, has recently been introduced as a myocardial perfusion agent and is now also showing very promising results in parathyroid scintigraphy. The results of 201Tl/99mTc-pertechnetate and 99mTc-MIBI/99mTc-pertechnetate subtraction scintigraphy, ultrasonography and computed tomography are presented in a series of 43 patients operated on for hyperparathyroidism. All four imaging modalities were confirmed to be reliable, scintigraphy being the most accurate. Sensitivities ranged from 81% to 95%, that of 99mTc-MIBI being the highest. Moreover this tracer, which has more favourable physical and also biochemical properties, yielded images of superior quality. This allowed localization of the lesion by visual inspection only in as many as 86% of the patients with positive 99mTc-MIBI/99MTc-pertechnetate subtraction scintigraphy. We believe that the higher sensitivity, superior image quality and lower cost of 99mTc-MIBI imaging will make 99mTc-MIBI the new radiopharmaceutical of choice for parathyroid scintigraphy (when one take into account the stability of labelling with large activities it is possible to perform three or four cardiac studies together with one parathyroid scintigraphic examination using one lyophilized vial).

Adenoma↗

Preparation and clinical evaluation of technetium-99m dimercaptosuccinic acid for tumour scintigraphy.

We describe a simple method of pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] preparation for the imaging of medullary carcinoma of the thyroid using commercially available kits. 99mTc(V)-DMSA is available at high pH (approximately 7.5) by adding NaHCO3 solution in the presence of a small amount of reducing agent (SnCl2). On the other hand, trivalent 99mTc-DMSA [99mTc(III)-DMSA] can be obtained at low pH (below 3) in the presence of an excess amount of reducing agent. In the clinical evaluation of a patient with a medullary carcinoma of the thyroid, only 99mTc(V)-DMSA revealed an area of intense accumulation.

3-Iodobenzylguanidine↗

Autoradiography and density gradient separation of technetium-99m-exametazime (HMPAO) labelled leucocytes reveals selectivity for eosinophils.

Technetium-99m-Exametazime (HMPAO) is widely used for radiolabelling leucocytes for localization of infection. The subcellular distribution of radionuclide in the labelled cells and the distribution of radioactivity among the leukocyte population are incompletely understood. Frozen section autoradiography was used to determine quantitatively the distribution of 99mTc in leucocytes labelled with 99mTc-Exametazime. Sections of rapidly frozen suspensions of labelled leucocytes in plasma were autoradiographed on Ilford K2 emulsion and stained with haematoxylin and eosin. Neutrophils, eosinophils and mononuclear cells were separated by Percoll density gradient centrifugation. Cell nuclei were isolated by a rapid cell-breakage and fractionation method. In a typical experiment mean grain densities [grains/100 microns2 (ESD)] over cells were: eosinophils 31.2 (18.4), neutrophils 3.5 (3.5), mononuclear cells 4.2 (5.1). Mean grain numbers per cell (ESD) were: eosinophils 13 (6.8), neutrophils 1.3 (1.3), mononuclear cells 1.1 (1.3). These findings were confirmed by separation of labelled leucocytes on discontinuous density gradients. In four separation experiments, the mean activity-per-cell ratio for eosinophils to neutrophils was 10.1 (4.8):1, and for eosinophils to mononuclear cells, 14.1 (6.7):1. The subcellular distribution of the label was investigated using image analysis of autoradiographs and cell fractionation. This revealed no selectivity for nuclear or extranuclear compartments. It may be concluded that 99mTc-Exametazime has strong selectivity for eosinophils over other leukocytes but no selectivity for nuclear/cytoplasmic compartments.

Animals↗

Different kinetics of lung clearance of technetium-99m labelled diethylene triamine penta-acetic acid in patients with sarcoidosis and smokers.

The rate of clearance from the lungs of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (99mTc-DTPA) is often increased in interstitial lung disease as well as in smoking. In smokers a bi-exponential clearance course of 99mTc-DTPA when measured over 3 h has previously been shown. This study was performed to compare the kinetics of clearance of 99mTc-DTPA, measured for 3 h, in sarcoid patients and healthy smokers. Forty-one never-smoking patients with sarcoidosis and radiological signs of intrathoracic disease were studied. The results were compared with those of 16 healthy current smokers and of 14 healthy never-smokers reported previously. A mono-exponential clearance equation described the clearance in 22 of the sarcoid patients and all normal never-smokers, but with a shorter average tracer half-life in the patients (P < 0.05). In 19 patients and all smokers a bi-exponential equation gave a significantly better curve fit. The rate of clearance of the slow component was higher in patients with sarcoidosis than in smokers (P < 0.05). The fraction of the tracer cleared by the fast clearance component was smaller in patients with sarcoidosis than in smokers (P < 0.01). Differences in kinetics of clearance of 99mTc-DTPA in sarcoidosis and smoking could thus be demonstrated, suggesting that the abnormal clearance is caused by diverging pathophysiological mechanisms.

Adult↗

Does technetium-99m bicisate image local brain metabolism in late ictal temporal lobe epilepsy?

Ictal increase in regional cerebral blood flow as judged by single-photon emission tomography (SPET) is a common phenomenon during focal epileptic seizures. Up to 2 min postictally, regional hyperperfusion is a consistent finding with technetium-99m hexamethylpropylene amine oxime (HMPAO) in temporal lobe epilepsy. A new 99mTc-labelled lipophilic cerebral blood flow imaging agent, bicisate, has considerably longer radiochemical stability and yields better image quality than 99mTc-HMPAO. In this report, we present the case of a 21-year-old female patient with temporal lobe complex partial seizures. Magnetic resonance imaging revealed right hippocampal sclerosis. A dose of 550 MBq of 99mTc-bicisate was injected 35 s after the onset of a seizure during intracranial EEG-videotelemetry. At the moment of injection, subdural EEG demonstrated the beginning of late ictal discharges and postictal suppression in the right temporomesial areas. Late ictal SPET images showed marked right fronto-temporo-parietal hypoactivity. The interictal SPET study clearly showed right frontotemporal hypoactivity. These preliminary data suggest that 99mTc-bicisate shows late ictal/early postictal hypoactivity which might represent the primary change in neuronal metabolism rather than the secondary change in cerebral blood flow.

Adult↗

The effect of hydration on the dose to the urinary bladder wall during technetium-99m diethylene triamine penta-acetic acid renography.

A spherical bladder dynamic model for the estimates of the radiation dose to the bladder walls from intravenously injected radionuclides was implemented to investigate in theory the effect of hydration on the reduction of the bladder dose in technetium-99m diethylene triamine penta-acetic acid (99mTc) DTPA renography. This model gives due consideration to the variation with time of the urine flow rate to the bladder, following a known fluid load. According to the model, the estimated dose depends on the renal function, the fluid load, the time elapsed from the fluid load to the i.v. DTPA injection, the micturition volume and the residual urine volume. Experimental data concerning the values of these parameters for normal individuals were obtained from the literature. Calculations cover the time period from i.v. injection up to the time of the ninth postinjection void. Results show that the patient's condition of hydration is critical for the radiation protection of the bladder. It is shown that optimum combinations of the values of the parameters involved in the calculations exist, which minimize the radiation dose. On the basis of these results, a general protocol is proposed, referring to the hydration conditions under which the renal dynamic study may be normally carried out, with a minimal absorbed dose to the bladder walls (less than 0.045 mGy/MBq).

Adult↗

Prediction of reversible perfusion defects by quantitative analysis of post-exercise electrocardiogram-gated acquisition of technetium-99m 2-methoxyisobutylisonitrile myocardial perfusion scintigraphy.

The aim of this study was to assess the reliability of the quantitative analysis of regional wall thickening with electrocardiographic-gated technetium-99m 2-methoxyisobutylisonitrile (SESTAMIBI) in predicting the reversibility of stress-induced perfusion defects. The assumption was that a preserved resting wall thickening in a segment with stress-induced perfusion defect would predict normal resting perfusion. Twenty-five patients with suspected coronary artery disease underwent planar stress-rest SESTAMIBI scintigraphy. The wall thickening was quantitatively evaluated as percentage increase in counts from diastole to systole; a ratio defined as the wall thickening index (WTI) between patient and normal profile (mean - 2 SD) below 1 was considered abnormal. Improvement of the perfusion pattern at rest was observed in 76% (54/71) of segments with a stress-induced perfusion defect; 90% of these segments had a (WTI) greater than 0.8. Five segments (9%) showed fixed perfusion defects despite a WTI value greater than 0.8. In conclusion, quantitative analysis of regional wall thickening by electrocardiographic-gated SESTAMIBI identifies segments with reversible perfusion defects; this may overcome the need for studies at rest and may direct the detection of hypoperfused but viable myocardium.

Coronary Disease↗

Comparison between exercise and trans-oesophageal atrial pacing in patients with coronary artery disease: technetium-99m methoxy isobutyl isonitrile simultaneous evaluation of ventricular function and myocardial perfusion.

In this study we compared the results of exercise and trans-oesophageal atrial pacing (TAP) technetium-99m methoxyisobutyl isonitrile (99mTc-SESTAMIBI) cardiac imaging in the evaluation of left ventricular (LV) function and myocardial perfusion in patients with angiographically proven coronary artery disease. Ten patients (8 men and 2 women, mean age 59 +/- 6 years) were submitted to 3 separate injections of 99mTc-SESTAMIBI, one under control conditions, one after exercise and one after TAP. LV ejection fraction, as measured by electrocardiogram (ECG) gated first pass, decreased from 49 +/- 5% under control conditions to 42 +/- 6% during exercise (P less than 0.05 versus control) and to 43 +/- 8% during TAP (P less than 0.05 versus control and insignificant change versus exercise). Segmental myocardial perfusion analysis was performed on a total of 150 myocardial segments. On both exercise and TAP 99mTc-SESTAMIBI studies, 103 segments (69% of the total) were normal, 32 (21%) had reversible, and 15 (10%) irreversible, perfusion defects. Relative regional tracer uptake was not statistically different between exercise and TAP in normal regions (91.1 +/- 9.1% versus 90.7 +/- 8.5%, respectively), in regions with reversible (61.9 +/- 12% versus 62.4 +/- 10.4%, respectively) and irreversible perfusion defects (55.8 +/- 7.8% versus 58.8 +/- 9.5%, respectively). Our results demonstrated that 99mTc-SESTAMIBI TAP cardiac imaging shows similar results to 99mTc-SESTAMIBI exercise myocardial scintigraphy in the assessment of LV function and myocardial perfusion in patients with coronary artery disease.

Cardiac Pacing, Artificial↗

Amplitude analysis of stress technetium-99m methoxy isobutylisonitrile images in coronary artery disease.

To determine the role of rest and stress gated technetium-99m methoxyisobutylisonitrile (sestamibi), in the detection of coronary artery disease, routine Fourier analysis of these images was performed with the best septal left anterior oblique (LAO) position of 20 patients (17 men, 3 women; aged 40-75 years) who also underwent rest or redistribution/stress single photon emission tomography (SPET) (99mTc-sestamibi and Thallium-201), gated blood pool imaging and coronary angiogram. There were 6 patients with single-vessel disease, 6 with two-vessel disease, 4 with three-vessel disease, 2 with coronary spasms, 1 with a patent graft and 1 with anginal episodes but a normal angiogram result. Three normal volunteers (2 women, 1 man; aged 24-26 years) also had rest and stress gated blood pool as well as rest and stress gated 99mTc-sestamibi imaging. Rest and stress 99mTc-sestamibi amplitude and phase images depicted regional myocardial wall shortening from the outer layer of the myocardium to the center of the left ventricle as follows: a high amplitude halo of maximal negative count rate variation; a circular thinner halo of negligible amplitude; a central region of maximal positive count rate variation, as the images evolved from end-diastole to end-systole. Similar patterns with regional differences represented abnormal myocardial wall shortening. 99mTc-sestamibi and 201Tl SPET images were in agreement in 90% of the patients and 92% of myocardial regions. 201Tl SPET detected 83% of angiographically proven lesions, as compared with 80% for 99mTc-setamibi SPET and 80% for the amplitude images. The amplitude images demonstrated a larger number of other abnormalities not predicted on the angiogram, probably because they were able to detect regions with a potential for flow improvement and transient regional wall shortening abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of coronary reperfusion on technetium-99m methoxyisobutylisonitrile uptake by viable and necrotic myocardium in the dog.

Technetium-99m hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) distribution is flow-dependent, permitting the imaging of coronary perfusion defects. However, the behaviour of this tracer in viable and necrotic tissues within the ischaemic area at risk is still being debated. In a clinically relevant canine model, dogs were submitted either to a 24-h permanent occlusion (group 1) of the left descending coronary artery (LAD) or to a 90-min LAD occlusion followed by 22.5 h reperfusion (group 2). 99mTc-MIBI and radiolabelled microspheres were injected 3 h before sacrifice. After delimiting the area at risk and the infarct by Evans blue perfusion and triphenyltetrazolium chloride staining, heart slices were imaged by scintigraphy and tissue radioactivity measured in a gamma-counter. In the necrotic area of both groups, the 99mTc-MIBI distribution was proportional to the myocardial blood flow, approximating a 1:1 ratio (identity line slope 1, intercept 0) with highly significant correlation coefficients (group 1 r = 0.87, group 2 r = 0.86), whereas in the viable-ischaemic area of both groups, the data points are widespread above and below the identity line, indicating both over- and underestimations of blood flow in these tissue areas. These results were more pronounced following reperfusion as compared with permanent occlusion. Multiple linear regression analysis confirms differences (P less than 0.001) in 99mTc-MIBI distributions between the viable-ischaemic and the necrotic zones. Delineation of the ischaemic area at risk was possible only with permanent occlusion. A hypoperfused area was observed after reperfusion but differs from the anatomical infarcted area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Optimising technetium 99m diethylene triamine penta-acetate lung clearance in patients with the acquired immunodeficiency syndrome.

Pneumocystis carinii pneumonia (PCP) has become a major cause of morbidity and mortality due to infectious diseases, largely as a result of the acquired immunodeficiency syndrome (AIDS) epidemic. Since the mortality from recurrent infection is between 40% and 60%, early diagnosis and therapy are the keys to survival. The role of technetium 99m diethylene triamine penta-acetate (DTPA) aerosol pulmonary clearance was studied in 81 patients with AIDS. The mathematical technique of curve stripping was found to be the optimal method of analysis and to provide an overall sensitivity of 94% for the detection of interstitial pneumonitis. The procedure was superior to standard pathology parameters and radiography and more convenient than gallium 67 scintigraphy.

Acquired Immunodeficiency Syndrome↗

Technetium 99m SESTAMIBI myocardial perfusion imaging: comparison between treadmill, dipyridamole and trans-oesophageal atrial pacing "stress" tests in normal subjects.

The purpose of this study was to determine the blood clearance, myocardial uptake and heart/lung and heart/liver ratios of technetium 99m methoxyisobutylisonitrile (99mTc-SESTAMIBI) following 3 different types of cardiac stimulation in normal subjects: treadmill stress (STRESS), intravenous administration of dipyridamole (DIP) and trans-oesophageal atrial pacing (TAP). Ten normal volunteers were submitted to 3 injections of 99mTc-SESTAMIBI (10 mCi/70 kg, separated by an interval of 7 days) following STRESS (standard Bruce protocol), DIP (0.142 mg/kg.min during 4 min) and TAP procedures. Blood samples were collected from 1 to 60 min after each 99mTc-SESTAMIBI injection. Planar imaging was performed at 5, 30 and 60 min. Blood retention (percentage of injected dose at 1 min) was 56% +/- 4%, 24% +/- 4% and 38% +/- 6% for STRESS, DIP and TAP, respectively (P less than 0.001). Myocardial uptake was similar for the 3 procedures while the heart lung ratio at 60 min was 3.1 +/- 0.5, 3.8 +/- 0.6 and 3.2 +/- 0.5 for STRESS, DIP and TAP, respectively. Heart/liver ratio at 60 min was 1.9 +/- 0.5, 1.3 +/- 0.3 and 1.1 +/- 0.2 for STRESS, DIP and TAP, respectively (P less than 0.001). These results demonstrated that the 3 types of cardiac stimulation show good imaging parameters with 99mTc-SESTA-MIBI.

Adult↗

How good is technetium-99m mercaptoacetyltriglycine indirect cystography?

The aim of the present study was to estimate the sensitivity of indirect radionuclide cystography (IRC) performed with technetium-99m mercaptoacetyl-triglycine (MAG3), in comparison with the micturition cystourethrography (MCUG) and direct radionuclide cystography (DRC), for the diagnosis of vesicoureteric reflux. Two groups of patients were selected: group I comprised 40 children who underwent IRC during the acute phase of urinary tract infection and an MCUG 6 weeks later; group II comprised 42 (other) children with known reflux, who underwent IRC and DRC during follow-up. Taking as the reference the total number of refluxing kidneys detected by means of any cystographic technique, 99mTc-MAG3 ICR missed two-thirds of the refluxing kidneys. Most of the small refluxes were missed, but so too were 50% of the major refluxes. Taking as the reference 99mTc dimercaptosuccinic acid (DMSA) scintigraphy, MCUG detected 91% of the patients with DMSA abnormalities on at least one kidney, DRC detected 95%, and IRC detected 46% and 43% respectively, in groups I and II. The use of 99mTc-MAG3 IRC as the sole technique for the detection of vesicoureteric reflux gives rise to an unacceptable number of false-negative results.

Adolescent↗

Reliability of low-frequency auditory stimulation studies associated with technetium-99m hexamethylpropylene amine oxime single-photon emission tomography.

Development of auditory stimulation tests associated with single-photon emission tomography (SPET) shows evidence of variations in perfusion related to the stimuli. Three brain SPET examinations with technetium-99m hexamethylpropylene amine oxime were performed on eight right-handed adults with normal hearing, the first one without stimulation and the other two associated with a 500-Hz/30-dB stimulation of the right ear. Temporal regions of interest covering auditory areas, as well as parietal ones (internal control), were drawn on three successive coronal slices. A cortico-cerebellar index R was calculated, and the variation in activity was defined for each subject using the ratio R poststimulation--R prestimulation/R prestimulation. A significant increase in the temporal cortex count occurred in all subjects. This increase was bilateral, except for one subject in whom it was not significant on the right side. This result recurred during the second stimulation study. Overall the response of the left temporal cortex was stronger, although the asymmetry was not significant. The asymmetry repeated itself after each stimulation. The perfusion response is globally reliable in our study. We must ascertain how sensitive this test is with regard to deaf adults and adults with normal hearing before extending its use to children.

Acoustic Stimulation↗