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Technetium-99m mercaptoacetyltriglycine clearance: reference values for infants and children.

Six hundred and thirty-nine clearance studies performed in children aged 7 days to 19 years utilizing technetium-99m mercaptoacetyltriglycine (MAG 3) were retrospectively analysed. Standardized conditions for the investigation included: parenteral hydration (60 ml/hxm2 body surface) in addition to normal oral fluid intake, weight-related dose of 99mTc-MAG 3 (1 MBq/kg body weight, minimum 15 MBq) and calculation of clearance according to Bubeck et al. Of the 513 children, 169 included in this analysis could be classified as "normal" with regard to their renal function. Normal kidney function was judged by the following criteria: normal GFR for age, normal tubular function (absence of proteinuria and glucosuria), normal renal parenchyma (on ultrasonography, MAG 3 scan and intravenous pyelography), absence of significant obstruction and gross reflux (>grade I), no single kidney and no difference in split renal function >20%. Results showed increasing MAG 3 clearance values for infants during the first months of life, reaching the normal range for older children and adults between 7 and 12 months.

Adolescent↗

Assessment of myocardial perfusion and viability with technetium-99m methoxyisobutylisonitrile and thallium-201 rest redistribution in chronic coronary artery disease.

We compare thallium-201 rest redistribution and fluorine-18 fluorodeoxyglucose ([18F]FDG) for the assessment of myocardial viability within technetium-99m methoxyisobutylisonitrile (MIBI) perfusion defects in 27 patients with chronic stable coronary artery disease. The following studies were performed: (1) stress 99mTc-MIBI, (2) rest 99mTc-MIBI, (3) 201Tl rest-redistribution single-photon emission tomography, (4) [18F]FDG positron emission tomography. The left ventricle was devided into 11 segments on matched tomographic images. The segment with the highest activity at stress was taken as the reference (activity=100%). Perfusion defects at 99mTc-MIBI rest were classified as severe (activity<50%), moderate (activity 50%-60%) or mild (activity 60%-85%). Uptakes of [18F]FDG and rest-redistributed 201Tl were recognized as significant if they exceeded 50% of that in the reference segment. Among the 33 segments with severe 99mTc-MIBI rest perfusion defects, 21 had significant [18F]FDG and 10 significant rest-redistributed 201Tl uptake. As regards the 37 segments with moderate defects, [18F]FDG was present in 29 and 201Tl in 31, while of the 134 segments with mild defects, 128 showed [18F]FDG uptake, and 131, 201Tl uptake. In conclusion, there is an inverse relationship between the severity of 99mTc-MIBI perfusion defects and the uptake of rest-redistributed 201Tl and [18F]FDG. Both tracers are adequate markers of viability in mild and moderate defects; in severe defects 201Tl might underestimate the presence of viability as assessed by [18F]FDG.

Adult↗

Gastrointestinal activity following bone marrow scintigraphy with technetium-99m nanocolloid in patients with multiple myeloma.

Unexpected abdominal activity was registered later than 1 h post injection in technetium-99m bone marrow scintigrams of 13 multiple myeloma patients and of five controls. The activity was considered to be localised in the gastro-intestinal tract. It is attributed to accumulation of degradation products of the used nanocolloid tracer. Corresponding results are known in patients with inflammatory bowel disease when scintigraphy is performed with other radiopharmaceuticals.

Adult↗

Efficient one-step direct labelling of recombinant antibodies with technetium-99m.

High-affinity bacterially expressed antibody fragments can nowadays be cloned from established hybridomas or, more conveniently, isolated directly from antibody libraries displayed on filamentous phage. Such antibodies can be tagged with C-terminal peptide tags containing one cysteine residue, which represents a convenient functionalisation site for a number of applications, including technetium-99m labelling. Here we describe a simple one-step method for 99mTc labelling of cysteine-tagged recombinant antibodies with more than 50% radionuclide incorporation. The labelled antibodies displayed full retention of immuoreactivity and good stability.

Antibodies, Bacterial↗

Clinical utility of technetium-99m methoxisobutylisonitrile imaging in differentiated thyroid carcinoma: comparison with thallium-201 and iodine-131 Na scintigraphy, and serum thyroglobulin quantitation.

Recently, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) has been used to image thyroid carcinoma. A prospective study was performed to compare the efficacy of 99mTc-MIBI to thallium-201 (201Tl) scintigraphy in patients with differentiated thyroid carcinoma. The clinical utility of all radionuclide imaging modalities, i.e., 99mTc-MIBI, 201Tl, and iodine-131 Na (131I-Na), as well as serum thyroglobulin estimation, was evaluated. Thirty-four post-thyroidectomy patients (age range: 26-76 years) underwent 45 studies. Histopathologies studied included fourteen papillary, eight papillary-follicular, ten follicular, one Hürthle cell, and one medullary carcinoma of the thyroid. Following optimal stimulation of endogenous thyroid stimulating hormone (i.e, TSH 50 mU/ml), the patients underwent 201Tl and 99mTc-MIBI scintigraphy. Concomitant 131I-Na scintigraphy was performed and serum thyroglobulin levels were measured. Sixteen scan sets were performed prior to 131I-Na ablation therapy. Twenty-nine scan sets were performed following 131I-Na ablation therapy. The presence or absence of thyroid cancer was established by clinical, biochemical, radiologic, and/or biopsy findings. There was no significant difference in sensitivity and specificity of 201Tl scintigraphy versus 99mTc-MIBI scintigraphy in pre- and postablation studies. 131I-Na scintigraphy with determination of thyroglobulin level was sufficient in preablation studies. Among postablation patients, the addition of 99mTc-MIBI or 201Tl offered a higher diagnostic yield. Between the 201Tl and 99mTc-MIBI studies, there was a concordance of 69% in preablation and 97% among postablation patients (P=0.027). It is concluded that 99mTc-MIBI is a suitable alternative to 201Tl scintigraphy in thyroid carcinoma, especially following thyroidectomy and 131I-Na therapy. 131I-Na scintigraphy with serum thyroglobulin is adequate in both pre- and postablation patients. Among the post-131I-Na ablation patients, 99mTc-MIBI or 201Tl is extremely valuable for tumor localization, especially when the 131I-Na whole-body scan is negative. The combination of 99mTc-MIBI or 201Tl scintigraphy with 131I-Na and serum thyroglobulin offers the highest diagnostic yield.

Adult↗

The use of technetium-99m hexamethylpropylene amine oxime labelled granulocytes with single-photon emission tomography imaging in the detection and follow-up of recurrence of infective endocarditis complicating transvenous endocardial pacemaker.

In this case report we present a patient with a recurrence of subacute bacterial infectious endocarditis (IE) complicating a transvenous endocardial pacemaker. Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelled granulocytes were used for diagnosis and follow-up under medical treatment only, since surgical removal of the pacemaker lead was ruled out because of the general condition of the patient. Single-photon emission tomography (SPET) imaging displayed the active lesion previously suspected on echography. At the end of antibiotic therapy, SPET indicated a favourable disease outcome whereas echocardiographic abnormalities remained nearly unchanged. The medical treatment had eradicated the IE, and the patient did well for more than 1 year thereafter.

Aged↗

Effects of non-linear flow and spatial orientation on technetium-99m hexamethylpropylene amine oxime single-photon emission tomography.

The effects of two post-acquisition corrections on the visual and quantitative analysis of technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET) were determined. The corrections were for: (1) the improper spatial orientation of the patient data sets, and (2) the non-linear uptake of HMPAO across the blood-brain barrier. Reorienting the SPET image data sets removed observers' uncertainty in assessment caused by suspected head tilt; however, it increased their uncertainty due to perceived subtle perfusion deficits. Applying the correction to compensate for the decrease in uptake of HMPAO in high-flow regions resulted in an increase in the number of positive assessments. In a study involving 30 patient studies, intra-observer reliability increased from 62% to 83% (average of two observers) after applying both of the corrections, while inter-observer reliability improved from 62% to 81%. Quantitative methods of analysing the images are also affected by the corrections. In an ROI-based classification scheme, the quantitative assessments of more than one-half of the images are affected by the two corrections. These results need to be considered when comparing both quantitative and visual results from different studies in which the corrections may or may not have been applied.

Algorithms↗

Assessment of systolic wall thickening using technetium-99m methoxyisobutylisonitrile in patients with coronary artery disease: relation to thallium-201 scintigraphy with re-injection.

The results of resting planar ECG-gated technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) imaging were compared with those of thallium-201 (Tl) re-injection after exercise-redistribution scintigraphy in 20 patients (19 men, 1 woman, mean age 53 +/- 10 years) with angiographically proven coronary artery disease. Eight normal subjects (seven men, one woman, mean age 50 +/- 8 years) constituted the control group. In these subjects, only resting 99mTc-MIBI imaging was performed. The standardized percent count increase from end-diastole to end-systole was calculated as an index of wall thickening in 13 segments for each study. Regional wall thickening index (WTI) and 99mTc-MIBI uptake were significantly different (P < 0.05) among segments classified as normal, reversible defects, irreversible defects with increased tracer uptake after re-injection (Re+) or irreversible defects with unchanged tracer uptake after re-injection (Re-) on Tl imaging. Furthermore, WTI and 99mTc-MIBI uptake were significantly higher (P < 0.05) in Re- segments with moderate reduction of Tl uptake (> or = 50% of peak activity) than in Re- segments with severe reduction of Tl uptake (< 50% of peak activity). A significant relationship between WTI and the results of Tl scintigraphy was observed (rho = 0.71, P < 0.0001). The percentage of Re- segments with severe reduction of WTI was significantly higher compared to Re+ segments (64% vs 3%, P < 0.01). Furthermore, compared with moderate Re- segments, a significantly higher percentage of severe Re- segments showed a severe reduction of WTI (86% vs 48%, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗

Myocardial technetium-99m sestamibi single-photon emission tomography as a prognostic tool in coronary artery disease: multivariate analysis in a long-term prospective study.

To date several studies have evaluated the accuracy of thallium-201 myocardial scan in risk stratification of coronary artery disease (CAD), while reports using technetium-99m methoxyisobutylisonitrile (MIBI), a tracer particularly suited to single-photon emission tomographic (SPET) imaging, are lacking. To rectify this omission, a prospective study was started in 1988 and at present 176 consecutive, and thus unselected, patients have been enrolled. All of them have been submitted to stress-rest MIBI SPET for the diagnosis or evaluation of CAD; 147 patients (121 males and 26 females, aged 53 +/- 9 years) have completed a surveillance period of at least 36 months following the scintigraphic study (range 36-60 months, mean 43). Sixty-one patients had a documented previous myocardial infarction. The mean pre-test likelihood of CAD was 44% in the patients without prior infarction. The main anamnestic, clinical, EKG and scintigraphic findings were evaluated and statistically correlated with the incidence of ensuing cardiac events using both univariate (chi-square test) and multivariate analysis (logistic regression model). Twenty-nine patients suffered from a cardiac event during the follow-up period (i.e. three cardiac deaths, six myocardial infarctions and 20 cases of unstable angina). Statistical multivariate analysis identified MIBI scan as the only highly significant and independent prognostic predictor [P = 0.006, relative risk (RR) = 17.62]. In detail, the most important scintigraphic parameters were the presence of a reversible defect (P = 0.0089, RR = 5.11) and the extension of the stress perfusion defect (P = 0.0255, RR = 3.27). The presence of typical angina proved to be a slightly significant predictor (P = 0.051, RR = 2.45), while no other examined parameter showed a significant correlation with a bad prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina, Unstable↗

Upregulation of granulocyte CD11b (CR 3) after labelling with technetium-99m hexamethylpropylene amine oxime.

Today technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) is widely used for leucocyte scintigraphy, as 99mTc-HMPAO selectively labels granulocytes in mixed leucocyte suspensions. However, the influence of cell labelling on the expression of specific adhesion proteins has not been studied before. Therefore, we investigated five patients, four of whom had established Crohn's disease. We found that leucocyte labelling with 99mTc-HMPAO induces increased expression of the glucoprotein receptor CD11b on granulocytes, but it is not clear whether this upregulation affects the functional integrity of the granulocytes.

Adult↗

Imaging rheumatoid arthritis specifically with technetium 99m CD4-specific (T-helper lymphocytes) antibodies.

CD4 expressing T-lymphocytes are involved in the pathogenesis of rheumatoid arthritis, so the possibility of using radiolabelled CD4-specific antibodies to localise diseased joints was studied. Prospectively six patients with rheumatoid arthritis were investigated. Five of them received 200-300 micrograms of a 555 MBq technetium 99m CD4-specific antibody (MAX.16H5) and were examined with three phase bone scans. Max.16H5 (IgG1) was labelled according to the mercaptoethanol (Schwarz) method. Lymphocytes of one patient were isolated on a Ficoll-Hypaque gradient and labelled with the antibody in vitro. Scans were performed 1.5 h, 4 and 24 h post injection in anterior and posterior views. In all patients, diseased joints could be clearly imaged at as early as 1.5 h. The localisation of the diseased joints correlated (P less than 0.01) with the clinical signs, with the early methylene diphosphonate (MDP) scan (P less than 0.01) and only weakly with the late bone scan (P greater than 0.05). According to these data we conclude that 99mTc-labelled CD4-specific antibodies specifically image actively diseased joints in rheumatoid arthritis.

Antibodies, Monoclonal↗

Evaluation of technetium 99m cyclobutylpropylene amine oxime as a potential brain perfusion imaging agent for SPET.

Technetium 99m d,l-cyclobutylpropylene amine oxime (99mTc-CBPAO) has been developed as a brain-imaging agent for single photon emission tomography (SPET). 99mTc-CBPAO can be prepared using a simple labelling procedure suitable for routine clinical use. It has a high in vitro stability, as has been demonstrated by high-pressure liquid chromatography (HPLC) analysis. This shows that 3 h after labelling, less than 5% of the primary lipophilic complex which is capable of crossing the blood-brain barrier (BBB) converts to a secondary hydrophilic complex. Brain uptake (% dose/g wet tissue) of 99mTc-CBPAO, determined at 5 and 30 min after injection in two groups of six adult male Sprague-Dawley rats, was found to be 0.74 +/- 0.06 and 0.73 +/- 0.13 (mean +/- SD), respectively. These values are not significantly different from those obtained repeating the experiment with 99mTc-labelled hexamethylpropylene amine oxime (99mTc-HMPAO) (0.72 +/- 0.15 at 5 min and 0.88 +/- 0.24 at 30 min after injection). Since the rat brain uptake of 99mTc-CBPAO remained unchanged for a period of time suitable for tomographic study, the comparison of the two tracers was extended to two groups of ten patients. The latter were affected by neurological and psychiatric disorders and were studied with SPET. Human brain uptake (% dose/cc cortical grey matter) of 99mTc-CBPAO and 99mTc-HMPAO were 3.04 +/- 0.57 and 4.22 +/- 0.46 (mean x 10(-3) +/- SD x 10(-3), respectively, with a 32% significant difference. In two other groups of five patients, the first transit time-activity curves of the two tracers were compared.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Isolated ectopic lung uptake of technetium 99m methylene diphosphonate on bone scintigraphy in primary amyloidosis.

Pulmonary deposition of technetium 99m methylene diphosphonate was found on a bone scan of a patient with undiagnosed primary AL amyloidosis. Unusual clinical manifestations during the course of the disease led to a post-mortem diagnosis. The mechanisms for pulmonary and other ectopic soft tissue bone scan tracer depositions, as well as their significance in the diagnosis of amyloidosis, are discussed.

Aged↗

Measurement of left ventricular ejection fraction from gated technetium-99m sestamibi myocardial images.

Left ventricular ejection fraction (LVEF) and single-photon emission tomographic (SPET) imaging of the myocardium can be performed after a single technetium-99m sestamibi (MIBI) injection. Sixty patients underwent SPET imaging with MIBI. Immediately after SPET acquisition ECG-gated 99mTc-MIBI perfusion images were acquired using 24 planar images per R-R interval. A new method for measurement of LVEF from the ECG-gated 99mTc-MIBI perfusion images was developed. To validate the method, LVEF derived from MIBI perfusion images was compared with that from conventional radionuclide ventriculography in all 60 patients. Forty patients had evidence of myocardial infarction and 20 had normal perfusion on MIBI imaging. There was no statistically significant difference between LVEF computed from 99mTc-MIBI perfusion images and that from radionuclide ventriculography (r = 0.7062, P < 0.001). There was little difference associated with the technique (intraobserver variability r = 0.9772, P < 0.001). Interobserver variability was also good (r = 0.8233, P < 0.001). LVEF from 99mTc-MIBI perfusion images can be obtained at the same time as assessment of myocardial perfusion and in the same orientation and metabolism of the myocardium, thereby permitting more accurate and realistic prognosis and diagnosis in patients with coronary artery disease.

Adult↗

Estimation of glomerular filtration rate using chromium-51 ethylene diamine tetra-acetic acid and technetium-99m diethylene triamine penta-acetic acid.

Simultaneous measurements of the clearance rate of chromium-51 ethylene diamine tetra-acetic acid (51Cr-EDTA) and technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) were performed in 54 patients with a range of function between 9 and 176 ml/min. Using multiple blood samples the two clearance values correlated well (r = 0.97, SEE 8.6 ml/min) and DTPA clearance was higher by 2.9%. For each radiopharmaceutical the plasma clearance rates obtained using multiple blood samples were compared with those obtained with simplified methods, i.e., the 60-180 min two-sample method of Russell and the mono-exponential method with the Brochner-Mortensen correction. For both radiopharmaceuticals the clearance values correlated well with the Russell method (r = 0.99, SEE = 4.1 ml/min for EDTA; r = 0.99, SEE 4.9 ml/min for DTPA) and the mono-exponential method (r = 0.99, SEE 3.6 ml/min for EDTA; r = 0.99, SEE 3.9 ml/min for DTPA). The mean plasma clearance obtained using multiple blood samples did not differ significantly from that obtained with the Russell method, either in patients with a glomerular filtration rate (GFR) < 30 ml/min or in patients with GFR > or = 30 ml/min. The mean plasma clearance obtained using multiple blood samples differed significantly from that obtained with the mono-exponential method because of the great difference observed in patients with GFR > or = 30 ml/min. It is concluded that the Russell two-sample method after injection of 99mTc-DTPA is accurate enough for routine clinical use.

Chromium Radioisotopes↗

In vitro validation of a simple tomographic technique for estimation of percentage myocardium at risk using methoxyisobutyl isonitrile technetium 99m (sestamibi).

With the advent of technetium 99m-labeled myocardial blood flow agents, there is a need for a simple technique for quantitation of infarcted or jeopardized myocardium (IM). This study provides an in vitro validation of a simple technique based upon the analysis of three short-axis slices through the heart following emission computed tomography. All acquisitions were performed using a static cardiac phantom containing pertechnetate Tc 99m. Activity in the phantom was adjusted so that the count density and myocardial-to-background ratio were comparable to those observed in patients. Plastic insets (range of sizes = 4%-72% of myocardium) were used to simulate transmural infarctions. Eighteen studies were acquired, each over 180 degrees into a 64 x 64 matrix. Data were reconstructed using a Ramp Hanning filter with cut off at 0.7 times the Nyquist frequency. Short-axis slices of the myocardium were then generated, and representative apical (A), mid-ventricular (MV), and basal (B) slices were selected. For each slice, a circumferential profile was generated, and the average radius (R) was measured. The fraction (F) of the profile falling below a threshold value was considered to represent IM. Total IM was given by % IM = 100 x (RB FB + RMV FMV + 0.67 RA FA)/(RB + RMV + 0.67 RA), where the subscripts to R and F refer to the relevant short-axis slices. For a threshold set at 60% of peak, measured IM agreed closely with true IM (R2 = 0.98, measured IM = 1.01 x true IM - 1.35). Measurement of % IM was not distorted by variations in slice radius or in slice selection.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Semi-automatic quantification of regional cerebral perfusion in primary degenerative dementia using 99m technetium-hexamethylpropylene amine oxime and single photon emission tomography.

A new semi-automatic method for quantifying regional cerebral uptake of 99m technetium-hexamethylpropylene amine oxime (99mTc-HMPAO) was used to assess single photon emission tomograms from 5 normal subjects, 14 patients with Alzheimer's disease, 14 patients with dementia of frontal lobe type and 4 patients with dementia with motor neurone disease. Uptake in both posterior cortical regions, although not in other regions, was significantly lower (P less than 0.05) in Alzheimer's disease than in normal controls. Conversely in both dementia of frontal lobe type and dementia with motor neurone disease, uptake was significantly reduced (P less than 0.05) compared with controls in all anterior cortical regions but not in posterior regions. Numerical findings in each disease mirrored the pattern of reduced tracer uptake previously reported by visual assessment. Nine patients were re-examined after an interval of at least 1 year. Comparison of follow-up scans with original images showed significant decreases in mid-anterior, left anterior and left posterior cortical uptake (P less than 0.01) in patients with Alzheimer's disease and in left middle, left posterior and right posterior cortical uptake (P less than 0.01) in patients with dementia of frontal lobe type. The method of quantification may be a useful adjunct to the visual assessment of single photon emission tomograms.

Alzheimer Disease↗

Blood pool ventriculography with a new technetium-labelled complex (99mTc-DEPIC): a clinical evaluation.

A new, single bolus method of in vivo blood pool imaging using a technetium Tc99m phosphine isocyanide complex (DEPIC) which binds to pre-albumin was evaluated in volunteers (n = 4) and patients (n = 20). DEPIC was assessed for its safety and possible drug interactions. Its duration of action and quality of ventriculography were compared with imaging using standard in vivo red cell labelling (PYP) during two 3-h scanning periods 1 week apart. DEPIC had a mean plasma half-life of 3.3 h. The count rate over the left ventricle was initially 42% higher with DEPIC than with PYP. However, removal of DEPIC by the liver resulted in equivalent count rates by 1 h, and by 3 h PYP count rates were 22% higher than DEPIC. Immediately post injection mean (SD) difference in the left ventricular ejection fraction between the two methods was 2.4% (7.7%). Satisfactory DEPIC scans were obtained up to 2 h post injection, but by 3 h there was a mean difference of 13% (11.3%). DEPIC was found to be a safe alternative to red all labelling for blood pool angiography, suitable for routine work. The single bolus methodology and high initial count rates offer improved efficiency and a capability for truly emergency scanning.

Cyanates↗