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Technetium-99m labeling by means of stannous pyrophosphate: application to bleomycin and red blood cells.

A new technique of technetium labeling using stannous pyrophosphate instead of stannous chloride as reducing agent for pertechnetate has been applied to red blood cells and bleomycin. Results are so encouraging that this technique could be extended to other compounds capable of forming stable complexes with reduced technetium. No saline washes of red cells are necessary before or after the addition of pertechnetate. No purification step is performed after labeling of bleomycin.

Bleomycin↗

[Technetium 99m-diphosphate as an imaging agent in acute myocardial infarction (author's transl)].

To test the sensitivity and specificity of 99m-Technetium-Diphosphat myocardial scintigraphy in the diagnosis of acute myocardial infarction we examined the scintigrams of 53 patients admitted to our CCU. In all 38 patients with transmural myocardial infarction positive scintigrams with localized uptake of the tracer found. Myocardial imaging was performed 70--90 minutes after the intravenous injection of 15 mCi 99m-Technetium-Diphosphat in anterior and LAO position. The clinical value of the method for proving the presence or absence of a myocardial infarction is demonstrated on infarctions combined with bundle-branch block, pacemaker Ecg and on reinfarction. All normal cases in this group showed no tracer activity outside the bones. In unstable angina pectoris a faint but not localized tracer activity was found.

Acute Disease↗

Effect of technetium Tc 99m pertechnetate on bacterial survival in solution.

Survival of Staphylococcus epidermidis (10(2) organisms/ml) in solutions containing various levels of radioactivity was assessed. Six test preparations contained nonbacteriostatic 0.9% sodium chloride solution; four of these contained technetium Tc 99m pertechnetate (99mTcO-4) in various quantities (80, 250, 500, and 750 mCi). A fifth contained technetium that had decayed to an essentially nonradioactive form, and a sixth contained 0.9% sodium chloride solution only. Each of the six 20-ml solutions was inoculated with 2 ml of single-strength trypticase soy broth (TSB) containing 10(3) organisms/ml. At various times up to 12 hours after inoculation, 1-ml aliquots of each test solution were withdrawn and passed through 0.22-micron filters, thereby preventing further irradiation of the filtered organisms. The filters were incubated in single-strength TSB at 37 degrees C, and samples were examined for turbidity at 24, 48, and 72 hours. After 24 hours, 25 of the 36 sample tubes showed turbidity; after 48 hours, the turbid samples totaled 28. Bacteria in the two nonradioactive solutions remained viable throughout the 12-hour sampling period. Accumulated doses of radiation obtained in the 250-, 500-, and 750-mCi samples inhibited bacterial growth. To be a valid quality-control measure, sterility monitoring of prepared radiopharmaceutical dosage forms may need to be performed concurrently with their preparation.

Bacteria↗

A new Tc-99m-labeled myocardial imaging agent, hexakis(t-butylisonitrile)-technetium(I) [Tc-99m TBI]: initial experience in the human.

The cationic complex Tc-99m hexakis(t-butylisonitrile)technetium(I) (TBI) has been shown to concentrate in the myocardial tissue of several animal species. In the present preliminary study, the biodistribution of this material was examined in four normal subjects and in two patients with coronary artery disease. In three normal humans injected at rest, planar, tomographic, and gated myocardial images of high technical quality were obtained between 1 and 4 hr after injection. In one subject studied both at rest and during maximal exercise, the lung and heart activities were similar, whereas the liver-to-heart activity ratio was 3:1 at 60 min at rest compared with 1.8:1 with maximal exercise. In two patients with coronary artery disease, transient ischemia appeared as a perfusion defect up to 4 hr after injection at maximal exercise, and the image appeared normal when Tc-99m TBI was administered at rest. The images of areas of infarction appeared abnormal after injection at rest and after injection during exercise. Technetium-99m TBI is a promising myocardial imaging agent that may permit high-quality planar, gated, and tomographic imaging of myocardial ischemia and infarction.

Coronary Disease↗

[The use of simultaneous angiography to determine the signification of vascular images in renal scintiscans with technetium (author's transl)].

Combined angiography and renal scintiscans were used by the authors in an attempt to determine the signification of the images and vascular tracings obtained after intravenous injection of technetium (99mTc). They conclude that the scintiscan images are essentially the reflection of cortical vascularization and that its duration, as determined by the scintiscan, is roughly equal to the mean transit time of the indicator employed (Tc). Arterial stenosis cannot be demonstrated by scintiscans using technetium.

Adolescent↗

99m Technetium labelled heparin: potential value as a tracer of heparin activity in pharmacokinetic and biodistribution studies.

Pharmacokinetics and biodistribution of 99m Technetium (99mTc) labelled heparin were studies to assess its value as a tracer of heparin kinetics in comparison with unlabelled heparin. In vitro, the stability and labelling efficiency (98%) of the labelled drug were excellent and elution was minimal. In vivo, after I.V. infusion of the drug, there was no difference in the same animal between anticoagulant activity measurements and radioactive countings, both displaying a plasmatic biexponential pattern (T1 = 2.9 minutes, T2 = 76 minutes). Biodistribution studies showed primarily liver, spleen and kidney accumulation, with no thyroid uptake. The advantages of this technetium labelling may therefore be used for the heparin drug in various experimental and pathological situations even in humans.

Animals↗

Time dependence of iprofenin-labeling with technetium Tc 99m.

The incubation time required to attain 90% labeling efficiency (90% radiochemical purity) for technetium Tc 99m labeling of iprofenin (PIPIDA, Diagnostic Isotopes, Inc.), was investigated. Thirty iprofenin vials were prepared according to the manufacturer's instructions. Aliquots were withdrawn from 12 vials at times 0.5, 1, 2, 3, 5, 7, 10, 12, 15, 20, 30, 45, and 60 minutes after mixing. Aliquots were withdrawn from 18 vials at 1, 2, 3, 5, 7, and 10 minutes. Free pertechnetate and reduced/hydrolyzed technetium were isolated from aliquots with instant thin-layer chromatography and quantified with a scintillation well counter. Based on the 30 vials, a mean (+/- S.E.M.) of 5.83 +/- 4.32 minutes was required to attain 90% labeling efficiency. Using tolerance limits calculations, the incubation time required to be assured that 95% of vials have achieved 90% labeling is 16.8 minutes. It is concluded that 99mTc iprofenin vials should be incubated 17 minutes to be assured of 90% labeling efficiency.

Imino Acids↗

Complexes of technetium with hydroxycarboxylic acids: gluconic, glucoheptonic, tartaric, and citric.

Technetium complexes of several hydroxycarboxylic acids are used for medical imaging. To determine the oxidation state of technetium in these agents, we studied the reduction of pertechnetate (Tc-99) in 0.1 M solutions of four hydroxycarboxylic acids, using polarography and amperometric titration with Sn(II). In D-gluconate below pH 6, Tc(III) and Tc(V) complexes were identified with certainty, Tc(IV) questionably; at pH 6 to 10, Tc(IV) and Tc(V) were formed; above pH 10, Tc(III), Tc(IV), and Tc(V). In D-glucoheptonate below pH 6, Tc(III) and Tc(V) were formed, and questionably Tc(IV); at pH 6 to 10, Tc(V); above pH 10, Tc(III), Tc(V), and probably Tc(IV). In L-tartrate below pH 6, Tc(III), Tc(IV), and Tc(V) were formed; above pH 6, Tc(IV) and Tc(V). In citrate below pH 10, Tc(III), Tc(IV), and Tc(V) were formed; above pH 10, Tc(IV) and Tc(V). For all four ligands the initial product of reduction by Sn(II) at pH 3 to 9 was Tc(V). In freshly prepared tin-labeled imaging agents of this class, the oxidation state is probably Tc(V). Lower stable oxidation states exist, attainable by using reducing agents stronger than tin; these may show altered imaging properties.

Carboxylic Acids↗

Use of technetium-99m sulfur colloid to evaluate changes in reticuloendothelial function in dogs with experimentally induced chronic biliary cirrhosis and portosystemic shunting.

Technetium-99m sulfur colloid scintigraphy was used to study alterations of reticuloendothelial function in 7 dogs with experimentally induced biliary cirrhosis and portosystemic shunting. Scintigraphic studies were performed before and 6 weeks after common bile duct ligation. Radiocolloid plasma clearance rate was determined by measuring activity in plasma samples and by analyzing the rate of liver uptake on dynamic scintigraphic image sequences. Percentage of uptake in the liver, spleen, and lungs, as well as the ratio of hepatic-to-extrahepatic uptake, was determined from static equilibrium images. Relative to preoperative values, there were significant decreases in plasma clearance rate, percentage of liver uptake, and ratio of hepatic-to-extrahepatic uptake and significant increases in percentage of spleen and lung uptake on postoperative studies. The mechanism of technetium-99m-labeled sulfur colloid extraction by the liver is different from that of other radiocolloids; it does not require active phagocytosis or pinocytosis. Thus, liver uptake of this tracer principally reflects effective liver blood flow. Portosystemic shunting was documented in these dogs at the time of the postoperative radiocolloid scans, and we believed was responsible for the decrease in liver reticuloendothelial activity. Possible mechanisms for the increased splenic and pulmonary reticuloendothelial activities are discussed.

Animals↗

Technetium-99m-methylene diphosphonate scintimammography to image primary breast cancer.

UNLABELLED: Technetium-99m-methylene diphosphonate (MDP) uptake within breast lesions was investigated during routine presurgical bone scintigraphy in a cohort of women at high risk for cancer who were candidates for surgery or excisional biopsy. The aim was twofold: (a) to demonstrate positive 99mTc-MDP uptake in primary breast cancer and (b) to differentiate malignant from benign lesions. METHODS: Anterior and oblique lateral views of the breasts were acquired 0-4 min, 10-20 min and 2 hr after intravenous injection of 740 MBq of 99mTc-MDP in 200 women with elevated suspicion or proven diagnosis of breast cancer (Group 1) and in 80 women with other solid tumor types (Group 2). RESULTS: Physical examination and mammography revealed breast abnormalities in all Group 1 subjects. The mammographic findings were definitely positive for carcinoma in 120 patients, highly suspicious in 27 and indeterminate in 53. Breast cancer was later histologically diagnosed in 172 women (86%) and benign disease found in 28 women (14%). Of these patients, 158 (92%) showed focal uptake of 99mTc-MDP in the images collected 10-20 min after injection. This was found to be the best timing for imaging, with tumor-to-background ratios as high as 4.3 (mean +/- s.d. = 3.8 +/- 0.4). Two hr after injection, only 61 of the 158 (38%) malignant lesions were clearly detectable. CONCLUSION: Technetium-99m-MDP is concentrated by primary breast carcinoma 10-20 min after injection, enabling successful external gamma imaging. Scintimammography with 99mTc-MDP is an accurate test that differentiates malignant from benign breast lesions, particularly in patients with indeterminate mammograms.

Adult↗

Scintigraphic evaluation of pancreatic transplants using technetium-99m-sestamibi.

UNLABELLED: The purpose of this study was to evaluate the feasibility of using 99mTc-sestamibi in the assessment of pancreatic transplant. METHODS: Ten transplant recipients with a history of insulin-dependent diabetes mellitus were studied. Fourteen 99mTc-sestamibi studies were performed. Each patient was injected intravenously with 10 mCi of 99mTc-sestamibi. Two-second frames were obtained for 1 min, followed by serial dynamic and static images every 5 min for 30 min. Technetium-99m sestamibi studies, read by two nuclear medicine physicians, were correlated with clinicopathologic findings and compared to the ten 201Tl studies obtained in seven of these patients. RESULTS: On 99mTc-sestamibi images, normally functioning grafts showed adequate perfusion on the angiogram and good uptake followed by clearance on static images. Time-activity curves showed an initial upslope followed by a downslope after the initial uptake peak. The quality of 99mTc-sestamibi images was superior to those of 201Tl in five, similar in four and marginally inferior in one paired study. Technetium-99m-sestamibi was used for both flow and static images, whereas a 99mTc radiotracer angiogram was needed to accompany the 201Tl study. CONCLUSION: Our preliminary experience indicates that 99mTc-sestamibi helps evaluate pancreatic transplants and provides high count statistics, which result in better image quality and diagnostic detail. Extensive quantitative studies are being performed to further evaluate this agent's role in the clinical management of pancreatic transplant patients.

Adult↗

Reversible hypoperfusion of the cerebral cortex in normal-pressure hydrocephalus on technetium-99m-HMPAO brain SPECT images after shunt operation.

A man with dementia underwent radionuclide cisternography to establish the diagnosis of communicating hydrocephalus. Technetium-99m-HMPAO brain SPECT images showed marked hypoperfusion of both posterior cerebral cortices and three-dimensional displays that demonstrated perfusion defects at both of the posterior parietotemporal regions. A successful ventriculoperitoneal shunt operation was performed. Five and one-half months later, repeat three-dimensional display showed that the perfusion defects had resolved and a repeat brain SPECT image showed marked improvement of the hypoperfusion. This concurred with postoperative clinical improvement. Technetium-99m-HMPAO brain SPECT, which provides objective documentation of clinical recovery after surgery, could be routinely used to evaluate patients with normal-pressure hydrocephalus.

Cerebral Cortex↗

Technetium-99m labeled agents for skeletal imaging.

Technetium-99m labeled radiopharmaceuticals are the currently accepted agents of choice for skeletal imaging. Their introduction in 1971 literally initiated a new era in clinical bone scanning. The development of techniques for reducing Tc(VII) with Sn(II) provided the means for complexing this useful radionuclide with various phosphorus-containing compounds which were already known to be avid bone seekers. Long chain polyphosphates were widely used at first, but have been superceded by pyrophosphate and its organic analogs, the diphosphonates. Pyrophosphate is characterized chemically by P--O--P bonds, and the diphosphonates by P--C--P bonds. The chemical forms of their complexes with tin and technetium are not known, but they behave in many respects as weak chelates. Labeling efficiencies for 99mTc of 95% or better are routinely obtainable with both "in house" preparations and commercial kits. Proper molar concentrations and ratios of phosphorus-compound to tin are necessary for both for good labeling and to achieve optimum tissue distribution. Unreacted TcO4- and reduced unbound 99mTc are both potential contaminants in these preparations and must be considered in radiochemical quality control. In vivo tissue distribution and kinetics of the 99mTc-Sn-phosphorus compounds differ with details of preparation, category of agent, and clinical status of the patient. Blood clearance is multi-exponential, with skeletal uptake and urinary clearance accounting for most of the activity. Scanning may be started in 2 1/2 to 4 hr, at which time skeletal activity is on the order of 40 to 50% of the injected dose. The primary indication for bone scanning remains the detection of metastases from extraskeletal malignancies, and the 99mTc labeled agents are more sensitive than either radiographs or Fluorine-18 for demonstrating active lesions. In addition, many new applications in evaluating benign bone disease have widened the clinical scope of skeletal imaging which is rapidly becoming one of the most important studies in nuclear medicine.

Bone Diseases↗

Kinetics of a putative hypoxic tissue marker, technetium-99m-nitroimidazole (BMS181321), in normoxic, hypoxic, ischemic and stunned myocardium.

UNLABELLED: This study focused on the kinetics of the newly developed 99mTc-nitroimidazole, propyleneamine oxime-1,2-nitroimidazole (BMS181321) in the different setting of myocardial perfusion states and oxygenation levels, and compared the kinetics of BMS181321 with those of other technetium analogues. METHODS: The kinetics of BMS181321 were evaluated in isolated perfused rat hearts. Technetium-99m-hexamethylpropyleneamine oxime (HMPAO) and a non-nitroimidazole-containing analogue of BMS181321 (6-methyl propyleneamine oxime; PAO-6-Me) were used to compare their kinetics with those of BMS181321. RESULTS: BMS181321 cleared quickly from normoxic hearts and the retention in the myocardium 10 min after injection was 0.84% +/- 0.04% ID/g wet wt (mean +/- s.e.m.). In contrast, BMS181321 was retained after reperfusion when it was injected before ischemia; the uptake in the myocardium 10 min after reperfusion was significantly greater than in controls (23.9% +/- 3.9% ID/g wt, p < 0.05). CONCLUSIONS: These results indicate that 99mTc-BMS181321 is well trapped in ischemic myocardium and moderately trapped in hypoxic myocardium, but washed out quickly in stunned myocardium. The residence time influences the amount retained.

Animals↗

Technetium Tc 99m macroaggregated albumin lung scans. Use in chronic childhood asthma.

Serial roentgenograms and technetium Tc 99m macroaggregated albumin lung scans were done simultaneously in 30 bronchodilator-dependent asthmatic children and young adults during both relative remission and attacks of status asthmaticus. When chest roentgenograms showed air trapping and increased peribronchial vascular marking associated with persistent perfusion defects, the children benefited from further laboratory studies and continuous comprehensive therapy. Serial scans provided information about underperfusion that was not discernible either by roentgenograms or by usual blood gas studies. Also, lung scans are easier to obtain in children with long-standing asthma than are detailed pulmonary tests. In our study, technetium Tc 99m macroaggregated albumin scans showed persistent regional perfusion defects in 20 children wiht chronic asthma during relative remission and exacerbations.

Acute Disease↗

Histologically proven pressure sore-related osteomyelitis in the setting of negative technetium bone scans. Case report.

Pressure sores are common in patients with spinal cord injury, stroke or debilitating medical illness. Contiguous osteomyelitis is a well recognized complication of pressure ulcers, but remains a challenging diagnostic and management problem. Technetium bone scan is purported to be an extremely sensitive, although nonspecific diagnostic test for osteomyelitis. Indeed, a negative bone scan is thought to virtually exclude bone infection. We report three cases of pressure sore-related polymicrobial osteomyelitis where technetium bone scan was normal, yet bone biopsy demonstrated characteristic histopathologic changes of osteomyelitis. These cases raise questions regarding the sensitivity of bone scanning in the setting of pressure sores, and they demonstrate the need for further investigation into the correlation between nuclear medicine scan results and bone biopsy histopathology. Bone biopsy remains the gold standard for diagnosis of osteomyelitis, which can be present in bone underlying a pressure ulcer, even in the setting of a normal bone scan.

Adult↗

[Technetium TC 99m pyrophosphate myocardial scintigraphy in amyloidosis. Correlations with Doppler echocardiography].

Technetium 99m cardiac scintigraphy as practiced at present for diagnosing amyloisodid only provides a visual semi-quantitative assessment of uptake of the isotope. To improve the diagnostic accuracy of the method, the authors evaluated prospectively a personal technique of scintigraphy quantification based on early images obtained at the 20th minute in 15 patients with neuropathic amyloidosis. Doppler echocardiographic studies indicated that 9 patients had cardiac involvement whilst 6 were free of cardiac amyloidosis. The index of isotopic uptake (ratio of cardiac/abdominal uptake) was 0.44 to 1.58 in the first group and 0.09 to 0.31 in the second group. The correlation between the scintigraphic index and interventricular septal or posterior wall thickness measured by echocardiography was poor. These results obtained in 15 patients with neuropathic amyloidosis suggest that the scintigraphic index measured at the 20th minute is discriminatory and allows identification of those patients with cardiac involvement. On the other hand, the correlations with echocardiographic wall thickness are poor. Technetium 99m cardiac scintigraphy with this technique of quantification is a useful tool for diagnosing cardiac amyloidosis, especially when echocardiography is difficult to interpret.

Adult↗