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Sentinel lymph node biopsy in breast cancer using technetium-99m tin colloids of different sizes.

Axillary lymph node dissection (ALND) in the treatment of breast cancer is essential for predicting the prognosis and regional control of the tumor. At the same time ALND is associated with pain, numbness and sometimes lymphedema. Sentinel lymph node biopsy (SLNB) is a potential alternative procedure to conventional ALND in clinically node-negative breast cancer. In this study, we prepared the technetium-99m-labeled tin colloids with different sizes and compared their efficacy in SLNB. From September 1998 to February 2002, 184 clinically node-negative breast cancer patients were enrolled in the study at Keio University Hospital. Sentinel lymph nodes (SLNs) were identified by both blue dye and radioisotope. We prepared small-sized technetium-99m-labeled tin colloid (particle size: 200-400 nm in diameter). Regular-sized technetium-99m-labeled tin colloid is 400-1000 nm in diameter. In 74 patients, a SLNB was performed using regular-sized tin colloid; small-sized tin colloid was used in 110 patients. Subsequently, all of the patients were immediately followed by ALND. All dissected lymph nodes were evaluated by routine histopathological examination. The clinicopathological characteristics of the two groups were comparable. The lymphoscintigram detected SLN more frequently in the small-sized colloid group than in the regular-sized colloid group (P < 0.01). Small-sized tin colloid was also superior to regular-sized tin colloid in the SLN identification rate (97.3% versus 86.5%; P = 0.01). The mean value for ex vivo counts of the hottest sentinel lymph nodes of the small-sized colloid group was significantly higher than the counts of the regular-sized colloid group (P < 0.01). There was no significant difference in the accuracy between the two groups. It was concluded that SLNB using the small-sized tin colloid was technically feasible and provided higher detection and identification rates than the regular-sized tin colloid.

Adult↗

Technetium-99-labeled leukocytes in diagnosing diabetic osteomyelitis in the foot.

Hexamethylpropylamineoxine (HMPAO)-labeled leukocytes were studied to examine the scintigraphic significance of the procedure in diagnosing bone infection in patients with chronic nonhealing foot ulcerations. Fifty-two patients were scanned with Technetium-99-labeled white blood cells and scintigraphic results were compared with histological analysis, bone culture, and radiographic findings. Twenty-one patients demonstrated positive uptake with imaging and focal accumulation of leukocytes at the area of suspected infection. Sensitivity, specificity, and accuracy were calculated and found to be 86%, 90%, and 88%, respectively. Thirty-one members of the population were also scanned with Tc-99 methylene diphosphate (MDP) triphasic scintigraphy. Sensitivity equaled 91% and specificity was found to be significantly lower (40%) when compared with the leukocyte-labeled scans. Technetium-99 (HMPAO) leukocyte scintigraphs demonstrated a significantly higher specificity and accuracy rate when compared with Technetium-99 (MDP) triphasic scans.

Aged↗

Synthesis of a diaminedithiol bifunctional chelating agent for incorporation of technetium-99m into biomolecules.

The synthesis of a bifunctional chelating agent (BCA), 1, based on the diaminedithiol (DADT) ligand system, is described. The six-step synthetic sequence has been accomplished in 16% overall yield, affording 1, which contains a thiolactone as a reactive moiety, which permits direct coupling to nucleophiles without the formation of byproducts. The reactivity of 1 toward benzylamine and subsequent labeling of the ligand with technetium-99m has been evaluated as a model for preparation of various bioconjugates. Both coupling and exchange labeling occur in high yield under mild conditions, and competition reactions with diethylenetriaminepentaacetic acid (DTPA) indicate the superior stability of the technetium-99m-DADT complex. Preparation of BCA 1 thus provides a new avenue into technetium-labeled radiopharmaceuticals.

Chelating Agents↗

Reoxidation behavior of technetium, iron, and sulfur in estuarine sediments.

Technetium is a redox active radionuclide, which is present as a contaminant at a number of sites where nuclear fuel cycle operations have been carried out. Recent studies suggest that Tc(VII), which is soluble under oxic conditions, will be retained in sediments as Fe(III)-reducing conditions develop, due to reductive scavenging as hydrous TcO2. However, the behavior of technetium during subsequent reoxidation of sediments remains poorly characterized. Here, we describe a microcosm-based approach to investigate the reoxidation behavior of reduced, technetium-contaminated sediments. In reoxidation experiments, the behavior of Tc was strongly dependent on the nature of the oxidant. With air, reoxidation of Fe(II) and, in sulfate-reducing sediments, sulfide occurred accompanied by approximately 50% remobilization of Tc to solution as TcO4-. With nitrate, reoxidation of Fe(II) and, in sulfate-reducing sediments, sulfide only occurred in microbially active experiments where Fe(II) and sulfide oxidation coupled to nitrate reduction was occurring. Here, Tc was recalcitrant to remobilization with <10% Tc remobilized to solution even when extensive Fe(II) and sulfide reoxidation had occurred. X-ray absorption spectroscopy on reoxidized sediments suggested that 15-50% of Tc bound to sediments was present as Tc(VII). Overall, these results suggest that Tc reoxidation behavior is not directly coupled to Fe or S oxidation and that the extent of Tc remobilization is dependent on the nature of the oxidant.

Ferric Compounds↗

Solid-phase synthesis of peptide radiopharmaceuticals using Fmoc-N-epsilon-(hynic-Boc)-lysine, a technetium-binding amino acid: application to Tc-99m-labeled salmon calcitonin.

Labeling of proteins with metallic radionuclides for use in radiopharmaceuticals involves covalently attaching a bifunctional chelator. In principle, use of smaller peptides allows this chelator to be incorporated during solid-phase peptide synthesis (SPPS) with total site specificity. To realize the advantages of this approach, a lysine-hynic conjugate Fmoc-N-epsilon-(Hynic-Boc)-Lys was synthesized for incorporating the well-known technetium-99m-binding hydrazinonicotinamide ligand into peptides during SPPS. It was used to synthesize a technetium-99m-labeled salmon calcitonin with the hynic-linked amino acid in place of lysine-18. A trifluoroacetate group protected the hynic during alkaline oxidation to the cyclic disulfide and was readily removed by mild acid treatment. The peptide was efficiently labeled (91-98% radiochemical yield) with Tc-99m in the presence of tricine and SnCl(2) with high specific activity (>100 MBq/microg). The product showed good serum stability and specific affinity for human calcitonin receptors. Fmoc-N-epsilon-(Hynic-Boc)-Lys is a highly versatile technetium-binding amino acid for incorporation into peptides during SPPS. This allows total flexibility and control in the site of attachment and is suitable for a combinatorial approach to peptide radiopharmaceuticals.

Calcitonin↗

Somatostatin receptor-binding peptides labeled with technetium-99m: chemistry and initial biological studies.

The synthesis of peptides which possess a high affinity for the somatostatin receptor and contain a chelator for the radionuclide technetium-99m is described. The target compounds were designed such that they would form stable, oxotechnetium(V) chelate complexes in which the Oxorhenium(V) chelate complexes of these peptides were prepared as nonradioactive surrogates for the technetium complexes. Peptide oxorhenium complexes and Tc-99m complexes eluted closely upon HPLC analysis. The receptor-binding affinities of both the free and rhenium-coordinated species were measured in vitro. The binding affinities of the free peptides (Ki's in the 0.25 - 10 nM range) compared favorably with [DTPA]octreotide (Ki = 1.6 nM), which, as the indium-111 complex, is already approved for somatostatin receptor (SSTR)-expressing tumor imaging in the United States and Europe. Furthermore, the rhenium-coordinated peptides had binding affinities which, in many cases, were higher than those of the corresponding free peptides, with several complexes having a Ki's of 0.1 nM. Some of the more potent SSTR-binding peptides were labeled with technetium-99m and assessed in an in vivo study with tumor-bearing rats. The 99m Tc-labeled peptides prepared in this study should be useful as SSTR-expressing tumor-imaging agents due to their high SSTR-binding affinities, ease of preparation, and, because they are low molecular weight peptides, expected pharmacokinetics characterized by rapid tracer excretion from the body resulting in high-contrast images.

Amino Acid Sequence↗

Sentinel node biopsy with technetium-99m colloidal rhenium sulphide in patients with breast cancer.

BACKGROUND: Sentinel node biopsy is emerging as a technique to replace routine axillary lymph node dissection. The lymphatic mapping technique is still at a developmental stage and no standard technique exists. This study used technetium-99m colloidal rhenium sulphide with a mean particle size of 100 (range 50-200) nm for sentinel node mapping. METHODS: Eighty-seven patients with breast cancer, but no clinical evidence of axillary metastasis, were studied. One day before operation technetium-99m colloidal rhenium sulphide was injected at four points into breast tissue surrounding the tumour. Lymphoscintigraphy was performed 2 h after injection, and surgery was usually performed after 20 h. A hand-held gamma probe guided sentinel node biopsy. RESULTS: Lymphoscintigraphy revealed axillary hot spots in all patients. During operation, the sentinel node was identified in all 87 patients (100 per cent). The number of sentinel nodes per patient ranged from 1 to 5 (mean 2). Metastatic sentinel nodes were identified in 37 of 87 patients. There were no false negatives. CONCLUSION: This study suggests that technetium-99m rhenium sulphide is a suitable agent for sentinel node mapping in patients with breast cancer.

Adult↗

Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with (99m)technetium sestamibi scintigraphy.

OBJECTIVE: To determine the utility of ultrasonography for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, and to compare this method with (99m)technetium sestamibi scintigraphy. DESIGN: The results of ultrasonography for localization of enlarged parathyroid glands were determined in 120 consecutive patients with primary hyperparathyroidism and compared with findings at surgery (n = 86) and with the results of (99m)technetium sestamibi scintigraphy (n = 99). PATIENTS: All patients had biochemically documented primary hyperparathyroidism based on elevated serum calcium and 'intact' parathyroid hormone measured by immunoassay. Patients with prior parathyroid surgery or secondary hyperparathyroidism were excluded. MEASUREMENTS: High-resolution ultrasonography was performed by a single observer. (99m)Technetium sestamibi scintigraphy was performed using early and delayed (2-h) views, and correlated with simultaneous thyroidal 123I uptake in most patients. RESULTS: Ultrasonography detected putative enlarged parathyroid glands in 92 of 120 unselected patients (77%). It correctly predicted surgical findings in 64 of 86 patients undergoing surgery (74%), including 61 of 72 patients with solitary eutopic parathyroid adenomas (84%), but only two of eight patients with solitary ectopic adenomas, and only one of six patients with multigland parathyroid disease. Sestamibi scintigraphy was positive in 87 of 99 unselected patients (88%), a higher proportion than ultrasonography (P < 0.05), reflecting superior sensitivity for the detection of ectopic parathyroid adenomas. For 74 patients undergoing parathyroid surgery who underwent both imaging tests there was no statistically significant difference between ultrasonography and sestamibi scintigraphy in ability to correctly predict surgical findings (74%vs. 82%, respectively) or in positive predictive value (93%vs. 90%, respectively). However, sestamibi scintigraphy was clearly more sensitive for ectopic parathyroid adenomas, providing correct localization in 8/8 cases. When one test was negative, testing with the second method was usually positive, improving the likelihood of a positive result to 98% when both tests were employed. CONCLUSIONS: Ultrasonography can be a sensitive and accurate method for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, comparable in overall utility to sestamibi scintigraphy. These results suggest that a strategy of initial testing with one or the other method, followed by the alternate imaging test if the first test is negative, would provide correct parathyroid imaging in most patients without prior parathyroid surgery.

Adenoma↗

Comparison of the predischarge exercise thallium-201 perfusion defect after myocardial infarction with myocardium at risk measured during acute infarction with technetium-99m sestamibi imaging.

BACKGROUND: Exercise thallium-201 imaging provides a noninvasive estimate of the amount of myocardium presumed to be at risk of infarcting should a complete occlusion of the coronary stenosis occur. The relationship between the size of the exercise thallium perfusion defect and the extent of myocardium supplied by a diseased coronary artery has not been established. This study evaluates that presumed correlation. METHODS: Patients were injected intravenously with technetium-99m sestamibi during acute myocardial infarction before thrombolysis or conventional therapy to quantify the myocardium at risk. Twenty-six patients who underwent risk-area assessment subsequently underwent clinically driven, predischarge, submaximal exercise imaging with thallium-201. The exercise testing was performed on day 7 +/- 2 days. A conventional polar map display was used to quantify the perfusion defect. RESULTS: The myocardium at risk determined by technetium-99m sestamibi at the time of infarction was 30% +/- 20% of the left ventricle. The mean exercise thallium-201 defect was 34% +/- 22% of the left ventricle. The exercise defect tended to be slightly larger than the myocardium at risk (4% +/- 10% of the left ventricle, P =.05). There was a close correlation between the 2 measurements (r = 0.89, SE = 9.4, P <.0001). CONCLUSIONS: This study shows a close correlation between the myocardium "at risk" assessed acutely by technetium-99m sestamibi and the "presumed at-risk area" determined by thallium-201 imaging on predischarge exercise testing. This finding supports the concept that the size of the exercise thallium defect caused by coronary stenosis indicates the likely size of a myocardial infarction resulting from occlusion of that stenosis.

Adult↗

Measurement of myocardial blood flow velocity reserve with myocardial contrast echocardiography in patients with suspected coronary artery disease: comparison with quantitative gated Technetium 99m sestamibi single photon emission computed tomography.

BACKGROUND: The ability of high and low mechanical index (MI) imaging methods during myocardial contrast echocardiography (MCE) to assess the physiologic significance of coronary stenoses were compared with technetium 99m sestamibi single photon emission computed tomography (SPECT) in patients. METHODS: Intermittent ultraharmonic imaging (high MI) and power modulation angio (low MI) were performed during continuous infusions of the echo-enhancing contrast agent, Optison, at rest and after dipyridamole stress in 39 patients. Technetium 99m sestamibi SPECT was performed simultaneously. Images from the 3 apical windows were divided into 6 walls. Myocardial blood flow (MBF) velocity and MBF velocity reserve were quantified from pulsing interval versus acoustic intensity MCE curves in each wall using postprocessed images. RESULTS: Approximately 25% of the myocardial walls could not be analyzed from MCE because of artifacts. MBF velocity and MBF derived from both MCE methods increased significantly after dipyridamole in healthy patients (n = 143 and 129 walls for high and low MI, respectively), compared with those with either reversible (n = 11 and 10 walls for high and low MI, respectively) or fixed defects (n = 18 and 14 walls for high and low MI, respectively) on SPECT. Consequently, MBF velocity and MBF reserve were significantly greater for patients with normal perfusion. Receiver operator characteristic curves obtained for MBF velocity reserve provided a sensitivity and specificity of 82% and 87%, respectively, for high MI; versus 64% and 96%, respectively, for low MI imaging after uninterpretable images were excluded from analysis. CONCLUSIONS: Both high and low MI MCE imaging techniques can be used to determine the presence of perfusion defects as identified by technetium 99m sestamibi SPECT. Low MI imaging methods have a number of drawbacks that limit its sensitivity compared with high MI techniques.

Aged↗

Pulmonary lymphatic mapping in dogs: use of technetium sulfur colloid and isosulfan blue for pulmonary sentinel lymph node mapping in dogs.

Lung cancer is the most frequent cause of cancer death in the United States. The pattern of regional lymph node involvement is a major prognostic factor in a patient with nonsmall cell lung cancer. The accuracy of information obtained about the lymph node status of lung cancer patients can be potentially increased by sentinel node lymphatic mapping. This technique has been well studied in melanoma and breast cancer. It may be useful in increasing the detection of micrometastases and in decreasing the morbidity from complete mediastinal lymphadenectomy. We report an animal pilot study of pulmonary lymphatic mapping. The aim of our study was to gain experience in the surgical techniques for pulmonary sentinel node lymphatic mapping in an animal model prior to its application in humans. Technetium sulfur colloid and isosulfan blue dye were injected into different lobes of the lung followed by attempts to identify the sentinel node draining that specific portion of the lung. Technetium sulfur colloid identified the sentinel node in five of six dogs within 20 min after the radiotracer was injected into the lung parenchyma. Isosulfan blue dye identified the sentinel node in three of six dogs within 5 min. Both the agents are potentially useful, but we found greater technical ease in identifying the sentinel node with technetium sulfur colloid. Two single-institution pilot studies in humans have been performed. A multicentered study to validate and further refine this technique is necessary. Advanced pathologic techniques such as immunohistochemistry and reverse transcriptase-polymerase chain reaction can be used to enhance the accuracy of staging. This may facilitate proper application of novel therapeutic strategies to improve the current dismal prognosis of this disease.

Animals↗

SPECT imaging of gliomas with Thallium-201 and Technetium-99m-HMPAO.

Sequential Thallium-201 and Technetium-99m-HMPAO SPECT images were obtained from 7 patients with high-grade gliomas and 5 patients with low-grade gliomas. The histo-pathological tumor-type was verified from either biopsy specimens or resected tissue from surgery. There was an intense uptake of Thallium-201 in all high-grade gliomas. Compared to the contralateral hemisphere the mean uptake was 4.6 times higher. Low-grade gliomas showed only a marginally increased Thallium-201 uptake (1.4 times). No overlap existed between the two groups. There was no correlation between Technetium-99m-HMPAO uptake and tumor type. Thallium-201 appears to be a promising radiopharmaceutical for differentiating high- and low-grade gliomas, whereas Technetium-99m-HMPAO is not.

Adult↗

Heart imaging with cationic complexes of technetium.

The cationic technetium-99 complex trans-[99TC(dmpe)2Cl2]+, where dmpe is bis(1,2-dimethylphosphino)ethane or (CH3)2P-CH2-P(CH3)2, has been prepared and characterized by single-crystal, x-ray structural analysis. The technetium-99m analog, trans-(99mTc(dmpe) 2Cl2]+, has also been prepared and shown to yield excellent gamma-ray images of the heart. The purposeful design, characterization, and synthesis of this technetium-99m radiopharmaceutical represents a striking application of fundamental inorganic chemistry to a problem in applied nuclear medicine.

Animals↗

Erythrocyte radiolabelling: in vitro comparison of chromium, technetium, and indium in undamaged and heat damaged cells.

The stability of the commonly used red cell radio labels chromium-51, indium-(111 or 113m), and technetium-99m, within intact red cells and stroma and their distribution within the cell were compared in undamaged and heat damaged red cells in relation to the clinical use of heat damaged cells in the assessment of splenic function. Chromium-51 labelled haemoglobin both in undamaged and heat damaged cells; indium predominantly labelled haemoglobin in undamaged cells but labelled stroma in heat damaged cells, even when the cells were labelled before heating; technetium-99m predominantly labelled haemoglobin in undamaged cells but only labelled stroma in heat damaged cells if these were heated before labelling. Indium was more firmly bound by stroma prepared from heat damaged cells, and technetium-99m showed a high rate of elution both from cells and stroma, although this rate was lower for heat damaged cells.

Chromium Radioisotopes↗

A five year audit of the role of parathyroid hormone assays and thallium-technetium isotope subtraction scanning in the preoperative investigation of primary hyperparathyroidism.

An audit has been performed of the value of parathyroid hormone assays and thallium-technetium isotope scanning in the pre-operative investigation of 67 hypercalcaemic patients referred for surgery over a 5 year period. Parathyroid hormone assay by region-specific technique was found to have a diagnostic sensitivity of 75% (n = 52) whilst the more recent assay for the intact molecule was 97% sensitive (n = 34). Thallium-technetium isotope scanning was only 64% sensitive overall (n = 59), due in part to the small size of adenomata now being referred for surgery. This study confirms the role of the intact parathyroid hormone assay but questions that of thallium-technetium isotope scanning in standard protocols of investigation for hypercalcaemia.

Adult↗

Technetium-99m sestamibi/tetrofosmin myocardial perfusion scanning in cardiac and noncardiac sarcoidosis.

Left ventricular (LV) and right ventricular (RV) involvement in sarcoidosis must be firmly confirmed to determine patients' prognosis. We examined whether myocardial perfusion images using technetium-99m single photon emission computed tomography (SPECT) have a diagnostic benefit in the evaluation of biventricular involvement. Sixteen patients with sarcoidosis, aged 21-78 (54 +/- 12) years old, 5 males and 11 females, complicated with cardiac disease (cardiac sarcoidosis, n = 6) including tachyarrhythmias of ventricular origin (n = 5), atrioventricular block (n = 4), and congestive heart failure (NYHA > or = II, n = 1), were enrolled in this study. Myocardial SPECT using technetium-99m sestamibi or tetrofosmin was performed and semiquantitatively scored for comparison with 25 control subjects. Perfusion abnormalities were more frequently recognized in sarcoidosis (LV 5/16, 31% and RV 14/16, 88% vs. LV 0/25, 0% and RV 8/25, 32% in controls). LV involvement had a close correlation with atrioventricular block and with congestive heart failure, and multiple sites of RV involvement correlated with ventricular tachyarrhythmia of RV origin. Total number of defect segments were highest in cardiac sarcoidosis (18/30, 60% vs. 19/60, 32% in noncardiac sarcoidosis, and 11/150, 7% in controls, p = 0.0001), and semiquantitatively evaluated total LV and RV scores (ranging from 0 to 18) were higher than those of controls (15.1 +/- 1.8 vs. 11.4 +/- 3.0 in noncardiac sarcoidosis, and 9.0 +/- 5.0 in cardiac sarcoidosis) and exhibited a significant positive linear correlation with the RV ejection fraction (y = 19.8 + 1.83x, r = 0.786, p = 0.001). Biventricular SPECT using technetium-99m is clinically useful for the noninvasive evaluation of both ventricular involvements in sarcoidosis.

Adult↗

Technetium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology.

Technetium-99m stannous pyrophosphate was utilized for myocardial imaging in 202 patients admitted to the hospital with chest pain of uncertain etiology. One hundred and one patients had clinical and evolved electrocardiographic and enzymatic evidence of acute myocardial infarction. Ninety-six of these 101 patients had increased myocardial uptake of the technetium stannous pyrophosphate and positive myocardial scintigrams; there was nearly precise correlation between the ECG and myocardial imaging localization of the area of infarction for acute transmural myocardial infarctions. In the five patients with negative myocardial images the scintigrams were obtained after seven or more days had elapsed following the myocardial infarction. In the remaining 101 patients no clinical, ECG, or enzymatic evidence of infarction developed; 92 of these patients had negative myocardial scintigrams. Seven of the remaining nine patients were admitted with "unstable angina pectoris", and despite the absence of diagnostic ECG and enzyme evolution each of these patients had faintly and diffusely positive myocardial scintigrams. The remaining two patients had positive myocardial scintigrams but no definite ECG or enzymatic evidence of acute myocardial infarction. Thus the technetium pyrophosphate imaging technique appears safe, inexpensive and to correlate well with ECG and enzyme identification of the presence of infarction and with ECG localization of myocardial infarction. In addition the positive myocardial scintigrams in some patients with "unstable angina" suggest that there may be limited myocardial necrosis that is ordinarily undetected by ECG and enzymes in these patients. The incidence of false positive and false negative scintigrams appears to be small.

Angina Pectoris↗

The scoring system for early technetium-99m pyrophosphate scintigraphy as a method of evaluation of limiting the myocardial infarct size by thrombolysis.

The usefulness of a scoring system with early technetium-99m pyrophosphate scintigraphy as a method for evaluating the efficacy of myocardial preservation after thrombolysis was studied. The mean time from the onset of acute myocardial infarction to injection of the tracer was 5.6 +/- 1.5 h (range 2.8 to 11.9 h). All 36 patients underwent successful recanalization. Patients with strongly positive technetium-99m pyrophosphate uptake in anterior acute myocardial infarction had a significantly lower regional ejection fraction and a significantly larger thallium-201 defect score than those with 2+ positive results in chronic stage. Similarly, in inferior acute myocardial infarction, the thallium-201 defect score was significantly larger in patients with strongly positive uptake than in those with 2+ and negative uptake scores. In conclusion, strongly positive results in early technetium-99m pyrophosphate scintigraphy within 12h after the onset of acute myocardial infarction may indicate failure in limiting the infarct size by coronary thrombolysis.

Aged↗