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SPECT imaging of pediatric brain tumor with hexakis (methoxyisobutylisonitrile) technetium (I).

Technetium-99m-Hexamibi [Hexakis (methoxyisobutylisonitrile) technetium (i)] was developed as a myocardial perfusion agent with biologic properties similar to those of thallium-201 (201TI). As 201TI has recently been observed to be of value for the diagnosis of brain tumors when used in conjunction with single-photon emission computed tomography (SPECT) imaging technology, the possibility that the biologic similarity of the two radiopharmaceuticals extended to their affinity for tumors was tested. A 5-yr-old female patient with a brain stem astrocytoma showed marked focal uptake of 99mTc-Hexamibi at the site of tumor recurrence as defined by biopsy and prior 201TI/SPECT study. Tumor-to-normal cortex radioactivity ratios for the 99mTc-Hexamibi/SPECT study were 132:1 and the spatial resolution of the 99mTc-Hexamibi images was high. This observation suggests that 99mTc-Hexamibi merits further study as a potential agent for SPECT imaging of human brain tumors.

Astrocytoma↗

Endocardial monophasic action potential recordings for the detection of myocardial ischemia in man: a study using atrial pacing stress and myocardial perfusion scintigraphy.

In a study designed to appraise the use of monophasic action potentials (MAPs) to detect myocardial ischemia in endocardial recordings, changes in steady-state MAP duration were compared in recordings between normal and ischemic areas of myocardium identified by the use of a radionuclide tracer simultaneously with the MAP recording procedure. Single-site recordings were made from the left or right ventricular endocardium or both in 26 patients (32 recording sites) during atrial pacing up to angina threshold. Pacing was maintained for 2 minutes at each increment in heart rate and MAPs were recorded at the end of each 2-minute period. Perfusion defects produced by atrial pacing stress were detected using technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile injected at peak pacing stress. In 18 recordings from normally perfused areas of endocardium, MAP duration at 70% and 90% repolarization shortened by a mean (+/- SD) of 20.9 (3.7) msec and 22.0 (4.8 msec, respectively, for every 100 msec change in cycle length. This is in keeping with the effect of cycle length changes on the action potential duration. The extent of shortening was significantly greater (p less than 0.01) for 14 recordings from ischemic areas, being 32.0 (8.6) and 33.8 (9.7) msec, respectively, indicating the additional effect of localized myocardial ischemia. These results validate the applicability of the endocardially recorded MAPs for the detection of ischemia. Such methodology may provide a means of assessing therapeutic interventions aimed at the early phase of ischemia.

Action Potentials↗

99Tcm (v) DMSA and 67Ga-citrate imaging in patients with head and neck squamous carcinoma: a clinical and scintigraphic study.

Technetium-99m (99Tcm) (v) dimercaptosuccinic acid (DMSA) is a new tumour imaging agent which has been used to image medullary carcinoma of the thyroid and squamous cell carcinoma (SCC) of the head and neck. This study was undertaken to compare planar scintigraphy in patients with head and neck SCC using 99Tcm (v) DMSA and the established tumour imaging agent gallium-67 citrate (67Ga). Seventeen patients were studied of whom 16 had a head and neck malignancy. Clinical examination was more sensitive and accurate than 67Ga scintigraphy, which in turn was more sensitive and accurate than 99Tcm (v) DMSA in detecting patients with cancer, patients with primary tumours and patients with metastatic neck carcinoma. Neither 67Ga or 99Tcm (v) DMSA planar scintigraphy has any role to play in the routine evaluation at presentation of patients with head and neck SCC.

Adult↗

Technetium-99m dimercaptosuccinic acid uptake in long-term catheterized kidney. Comparison with renal function.

We studied 23 long-term catheterized kidneys in 14 patients. The uptake of 99mtechnetium dimercaptosuccinic acid (99mTc-DMSA) was measured at one- and two-hour intervals after injection, and the uptake was corrected for variations in renal depth. These values were compared with inulin, creatinine, and para-amino hippurate (PAH) clearances which were measured in each kidney by collecting urine through long-term catheterization. Correlation coefficient was obtained between PAH clearance corrected for the body surface area and the two-hour uptake of 99mTc-DMSA. The correlation coefficients between the two-hour uptake of 99mTc-DMSA and the clearance values are not significantly different from those between the one-hour uptake and the clearance values. Corrections of the uptake for variations in renal depth did not improve the correlation coefficients. The results show that 99mTc-DMSA is an excellent method to estimate the renal plasma flow and the one-hour uptake without correction for renal depth is clinically sufficient to evaluate the split renal function.

Aged↗

Imidazoles as well as thiolates in proteins bind technetium-99m.

99mTc is widely thought to directly bind proteins through thiolate groups of cysteine residues, resulting in Tc-cysteinyl-protein bonds. Chemical reduction of disulfide bonds in proteins is widely used to generate thiolates with the goal of increasing 99mTc binding. This strategy is used because most proteins contain no thiolates, but many do contain disulfide bonds. In this study, we have evaluated the hypothesis that imidazole groups of histidine are also involved in direct 99mTc binding to proteins. Human gamma-globulin was used as the model protein in these studies. The immunoglobulin was used (a) without reduction or was (b) treated with stannous ions to reduce disulfide bonds thereby increasing thiolate concentration. These proteins were used to evaluate the hypothesis that imidazole as well as thiolate groups bind Tc. The proteins were evaluated by (a) using free amino acids to compete with proteins for 99mTc and (b) by chemical modification of amino acid side chains. In addition, peptides known to contain either cysteine or histidine, but not both, were also successfully directly labeled with 99mTc. These results indicate that in proteins (and peptides) imidazole-containing groups as well as thiolate-containing groups bind Tc.

Amino Acids↗

Evaluation of radiography and isotopic scintigraphy for detecting skeletal metastases in breast cancer.

Experience with technetium-phosphate compounds for skeletal scintigraphy in patients with breast cancer was analysed. When tumours were 5 cm or less in diameter (T1-2N0-1M0) metastases were demonstrated by radiographs in 1-7% (2/114). However, when radiography did not demonstrate metastases, lesions were found by scintigraphy in 41-3% (19/46). When lesions demonstrated by scintigraphy at the same site as abnormalities regarded as "benign" by radiography were excluded, 23% (11/46) had scintigraphs strongly suggestive of metastases. It is proposed that routine radiographic skeletal survey for patients presenting with breast cancer be abandoned, and replaced by skeletal scintigraphy, chest radiography, and specific localised radiographs of lesions demonstrated by scintigraphy. It is suggested that with this policy the development of expertise in interpreting scintigraphs will be accelerated, the cost of pre-treatment assessment will be reduced, and clinical management rationalised.

Bone Neoplasms↗

Evaluation of right ventricular regional perfusion with technetium-99m-sestamibi SPECT.

To evaluate technetium-99m-sestamibi as a right ventricular perfusion imaging agent, 25 normal volunteers and 25 patients with suspected coronary disease were studied with both sestamibi and thallium-201 SPECT. All patients underwent cardiac characterization. Compared to thallium-201 images, visualization of the right ventricle was superior for sestamibi in all cases. After computer masking of the left ventricle, count profiles for each 6-mm right ventricular short-axis slice were extracted and plotted in a bull's-eye type polar map with images normalized to maximal right ventricular counts. On sestamibi right ventricular polar maps, 7 of 11 patients (64%) with right coronary stenosis had fixed or reversible inferior right ventricular defects. None of the 25 volunteers or patients without right coronary stenosis had right ventricular defects (true-negative rate = 100%). We conclude that sestamibi SPECT provides an accurate means to assess right ventricular regional perfusion, with data presentation and interpretation facilitated by the polar map display.

Adult↗

The effect of DMSA loading on the renal handling of technetium-99m in rats.

The renal handling of technetium-99m dimercaptosuccinic acid (99mTc DMSA) was studied in rats treated with high doses of nonradioactive DMSA to inhibit the renal uptake mechanism(s). A static scan was obtained 1 hour after the intravenous (iv) injection of 99mTc DMSA and the radioactivity in kidneys and bladder was calculated as a percentage of the injected amount. Total glomerular filtration rate (GFR) and effective renal plasma flow were also determined. Preloading with DMSA caused a fall in the renal accumulation of 99mTc DMSA together with a small increase in the amount excreted into the urinary bladder. Despite a stable GFR, the total amount of 99mTc DMSA handled by the kidneys (i.e., renal plus bladder activity) was reduced. These findings are compatible with the hypothesis that peritubular uptake and subsequent intracellular fixation are of importance in the renal accumulation of 99mTc DMSA. On the other hand, the radioactivity excreted into the urine probably stems from non-reabsorbed 99mTc DMSA initially filtered by the glomeruli.

Animals↗

Quantitative phase analysis of myocardial wall thickening by technetium-99m 2-methoxy-isobutyl-isonitrile SPECT.

Regional wall thickening was assessed by ECG-gated SPECT using technetium-99m 2-methoxy-isobutyl-isonitrile (99mTc-MIBI). For myocardial segments with an optimal short axis, regional count changes from end-diastole to end-systole were used to calculate the regional wall thickening. Functional images displaying amplitude, % wall thickening (% WT), and phase were generated by a fundamental Fourier analysis. In the control subjects, % WT analysis showed heterogeneous contraction among the left ventricular wall segments. The amplitude values showed a similar pattern to the %WT values. Phase images demonstrated that the timing of ventricular contraction was almost homogenous between the various wall segments. In the CAD patients, regional decreases in amplitude and %WT corresponding to zones of reduced perfusion were shown in the ischemic segments. Phase images also indicated asynchronous contraction in these segments. Phase analysis of regional wall thickening in 99mTc-MIBI scintigraphy seems to be useful for understanding regional myocardial function in combination with perfusion scanning.

Aged↗

[Scintigraphy with technetium dimercaptosuccinic acid (99 m TC DMSA). Contribution to the functional assessment of individual kidneys (author's transl)].

Renal uptake of 99m Tc DMSA was used to evaluate the renal function of 16 healthy subjects (controls) and 115 patients with various urinary tract diseases. Scintigraphic examination was carried out 6 hours after an intravenous injection of the product. In the 16 controls Tc DMSA uptake was 25.7 +/- 2.48% in the right kidney and 24.4 +/- 2.86% in the left kidney. In 36 patients with one single hypertrophied kidney, there was a correlation (r = 0.850) between creatinine clearance and Tc DMSA uptake, which was higher than in normal subjects (39.23 +/- 9.9%). In the group of 68 patients with unilateral (31) or bilateral (37) renal disease, a significant correlation (r = 0,725) was observed between kidney-to-kidney ratios of urea clearance and Tc DMSA uptake, so that renal impairment could be quantified. Quantitative scintigraphy did not appear to be of assistance in the remaining 11 patients with obstructive uropathy, as it overestimated renal function. The results obtained with 99 m Tc DMSA scintigraphy should be helpful in choosing between nephrectomy and conservative surgery and in assessing the degree of compensatory hypertrophy in single kidneys.

Creatinine↗

Simultaneous measurement of left ventricular function and perfusion.

A new radiopharmaceutical, methylisobutyl isonitrile (MIBI), has been developed as a technetium-99m-labelled alternative to thallium 201 for myocardial imaging. By virtue of the high specific activity of 99mTc, some 600 MBq may be administered as a 0.3 ml bolus, permitting the acquisition of a first-pass nuclear angiogram at rest and at peak exercise. The agent was assessed in ten sequential patients referred for routine cardiac catheterisation, who also underwent an exercise electrocardiographic (ECG) test. Good quality nuclear angiograms, planar perfusion and tomographic perfusion images were obtained; the results correlated well with the catheterisation data. Of 30 myocardial segments for which wall motion was judged normal/abnormal from the nuclear angiogram, results concordant with contrast studies were obtained in 27 (90%). In the case of the 50 segments analysed from the perfusion images, concordant results were obtained in 43 (86%) from the planar studies and in 42 (84%) from the tomographic studies. All normal segments were classified correctly.

Adult↗

Radionuclide imaging of soft tissue neoplasms.

Two classes of radiopharmaceuticals may be used for imaging tumors of the musculoskeletal system. The first is comprised of soft tissue or tumor specific agents such as gallium-67, bleomycin, and radionuclide-labeled antibodies, which may be useful for detecting and localizing these tumors. The other class of tracer is comprised of those with avidity for bone. The 99mTc-labeled-phosphate skeletal imaging compounds have been found to localize in a variety of soft tissue lesions, including benign and malignant tumors. In 1972, Enneking began to include bone scans in the preoperative evaluation of soft tissue masses. Later, he and his associates reported that these scans were useful in planning operative treatment of sarcomas by detecting involvement of bone by the tumors. Nearly all malignant soft tissue tumors take up bone-seeking radiopharmaceuticals, and bone involvement was indicated in two-thirds of the scans we reviewed. About half of benign soft tissue lesions had normal scans, but the other half showed uptake within the lesion and a few also showed bone involvement. Careful, thorough imaging technique is essential to proper evaluation. Multiple, high-resolution static gamma camera images in different projections are necessary to adequately demonstrate the presence or absence of soft tissue abnormality and to define the precise relationship of the tumor to the adjacent bone.

Bleomycin↗

Renal parenchymal damage on DMSA-scintigraphy in pelviureteric obstruction.

During a 1.5 year period 21 children were investigated with 99-m-technetium dimercaptosuccinic acid (DMSA) before operation for hydronephrosis due to pelviureteric obstruction. The age at investigation was 0.2-11.5 years. Fourty-two kidneys were examined. Hydronephrosis existed on the right side in 8 cases, left side in 9 and bilateral in 4 cases. Seventeen kidneys had no obstruction. The scintigraphy was interpreted as normal in 19 kidneys. Decreased isotope uptake was found in 23 kidneys and localized to the upper pole area in 19 kidneys, middle-lateral part in 7, lower pole area in 15 and the middle-medial part in 12 kidneys. There were no predominance for any part of the kidney to be affected by parenchymal damage. In 8 children investigated before the age of 1 year, 4 of 10 hydronephrotic kidneys revealed normal DMSA scintigram. DMSA scintigraphy delineates functioning renal parenchyma. DMSA scintigraphy delineates functioning renal parenchyma. It can be recommended as a routine method for evaluation of the renal parenchyma before surgery and for follow up studies in all ages of childhood.

Child↗

Renal handling of technetium-99m DMSA in rats with proximal tubular dysfunction.

The renal handling of technetium-99m dimercaptosuccinic acid ([99mTc]DMSA) was studied in rats before and after treatment with Na-maleate (2 mmol/kg i.v.). In the control period, when measured 2 hr after the intravenous injection of [99mTc]DMSA, 39.9% of the injected dose was in the kidneys and 14.6% was in the bladder. After Na-maleate treatment, only 6.4% of the injected dose of [99mTc]DMSA was retained in the kidneys while 37.9% was found in the bladder. Subsequent studies revealed that Na-maleate produced a fall in the glomerular filtration rate, the effective renal plasma flow, and a generalized proximal tubular dysfunction. The latter was characterized by polyuria and an increased excretion of glucose, protein, albumin, calcium, and inorganic phosphate. It was concluded that proximal tubular dysfunction markedly alters the renal handling of [99mTc]DMSA. Whether this augmented urinary excretion is due to an inhibition of reabsorption or an enhanced cellular efflux of [99mTc]DMSA remains to be answered.

Animals↗

Suppression by perchlorate of technetium-99m and iodine-123 secretion in milk of lactating goats.

Lactating goats were infused with either technetium-99m (99mTc) or iodine-123 (123I) together with chlorine-36 (36Cl) through an indwelling catheter previously placed in an external pudic mammary artery. The radioisotope infusions were repeated together with 100 mg of sodium perchlorate. There was a rapid transfer of 99mTc and 123I into milk, reaching a peak concentration 30 min after a 15-min infusion. The fractional secretion of 99mTc and 123I in milk was reduced by 70%-80% and 60%-66%, respectively, by perchlorate. The fractional secretion of 36Cl was not affected by perchlorate, and the shape of the 36Cl secretion curve differed from those of 99mTc and 123I, which were similar. It is probable, therefore, that the latter nuclides were secreted by a transport route different from that of chloride. Available data describing the secretion of 99mTc in human milk after pertechnetate administration was reviewed, and it was concluded that perchlorate pretreatment significantly reduced the secretion of 99mTc in human breast milk.

Animals↗

[Diagnostic accuracy of coronary artery lesion by 99mTc-MIBI exercise myocardial scintigraphy--containing the utility of simultaneous assessment of left ventricular function].

To determine whether technetium-99m hexakis-2-methoxy isobutyl isonitrile (99mTc-MIBI) myocardial scintigraphy is a superior method in the detection of coronary artery disease, exercise and rest 99mTc-MIBI planar and SPECT scintigraphy were performed on 27 patients with coronary artery disease. When 99mTc-MIBI (555 MBq (15 mCi)) was injected, first-pass radionuclide angiography (FPRNA) was simultaneously performed by a new mobile multicrystal gamma camera (SIM-400), and LV function (LVEF) was evaluated quantitatively. Visual semiquantitative detection of coronary lesions using 99mTc-MIBI images showed superior accuracy to that obtained using 201TlCl images. 99mTc-MIBI SPECT images were particularly useful in diagnosing LCX and RCA lesions. Moreover, the simultaneous assessment of perfusion and left ventricular function by 99mTc-MIBI FPRNA proved to be useful in the diagnosis of multi-vessel disease. In summary, 99mTc-MIBI SPECT scintigraphy with simultaneous assessment of left ventricular function showed better diagnostic accuracy than 201TlCl myocardial scintigraphy.

Aged↗

Technetium-99m direct radiolabeling of monoclonal antibody ior egf/r3.

Monoclonal antibodies (MAbs) are being widely used for imaging studies, coupled mainly with 99mTc. The antibody ior egf/r3 is a MAb against human epidermal growth factor receptor (hEGF-r), and we have developed a method for optimum labeling of this MAb with 99mTc. The reduction was performed with 2-mercaptoethanol (2-ME) at a molar ratio of 2000:1 (2-ME:MAb) and methylene diphosphonate as transchelant. The integrity of reduced MAb was checked by mean of native polyacrylamide gel electrophoresis (PAGE) and gel filtration chromatography on Superose 12 (purity >99%). Radio colloids remained lower than 2%, and the labeling efficiency was 98.5%. The number of sulfhydryl groups generated was quantified using Ellman's reagent and was found to be 6.65+/-0.69 per antibody molecule. In vitro stability studies in several challenging conditions (DTPA, human serum albumin and human serum) were performed, and no significant loss in binding percentage was seen. Radio receptor assay was used to test immunoreactivity of the reduced MAb. Both labeled and unlabeled MAbs were able to compete for binding to the hEGF-r with radioiodinated EGF. Biodistribution studies in BALB/c mice are reported.

Animals↗

Technetium-99m (v) dimercaptosuccinic acid uptake in patients with head and neck squamous carcinoma: experience in imaging.

A recently developed imaging agent, technetium-99m (v) dimercaptosuccinic acid (99mTc (v) DMSA), has been used to assess head and neck squamous carcinoma (SCC). We have prospectively studied 62 patients of whom 53 had a histologically proven head and neck SCC. The remaining nine had benign lesions. The results of planar imaging in patients with primary disease yielded an 85% sensitivity and 78% specificity. Planar imaging in patients with cervical lymphadenopathy revealed a 59% sensitivity. Nineteen patients also had single photon emission computed tomography imaging which improved the image quality, spatial resolution and sensitivity of the investigation. Twenty-seven patients were scanned before and after radiotherapy and, of these, 96% showed positive uptake in the salivary glands with no evidence of tumor recurrence. This study has shown 99mTc (v) DMSA imaging provides a cheap and rapid method of investigating head and neck SCC and further studies are necessary to evaluate its role in the management of patients with this disease.

Adult↗