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Biodistribution, dosimetry, and clinical evaluation of technetium-99m ethyl cysteinate dimer in normal subjects and in patients with chronic cerebral infarction.

Technetium-99m ethyl cysteinate dimer (ECD) has high initial cerebral uptake with slow clearance in nonhuman primates suggesting ideal characteristics for single photon emission computer tomography (SPECT) imaging. We evaluated the biodistribution, dosimetry and scintigraphic pattern of [99mTc]ECD in normal subjects and the accuracy of SPECT imaging in patients with chronic cerebral infarction. Sixteen normal subjects were injected with approximately 10 mCi of [99mTc]ECD. Anterior and posterior single-pass whole-body images were obtained at multiple times after injection. Blood clearance of the radiotracer was rapid, falling to 10.0 +/- 6.6% and 4.9 +/- 1.1% of the injected dose at 2 and 60 min, respectively. Brain uptake was 6.4 +/- 2.1% of the injected dose 5 min after injection. The critical organ was the urinary bladder. Technetium-99m ECD SPECT was performed with a rotating gamma camera in ten of the 16 normal subjects and 34 patients with clinical and CT evidence of chronic stroke. Thirty-three of the thirty-four patients had focal [99mTc]ECD abnormalities on SPECT (97.1%) based on visual inspection of the SPECT images. In summary, we obtained high quality SPECT images as a result of the optimal physical and biologic characteristics of the tracer. Technetium-99m ECD SPECT shows promise for the evaluation of patients with stroke.

Cerebral Infarction↗

Human biodistribution, dosimetry and clinical use of technetium(III)-99m-Q12.

UNLABELLED: Technetium(III)-99m-Q12, trans-(1,2-bis(dihydro-2,2,5,5-tetramethyl- 3(2H)furanone-4-methyleneimino)ethane)bis(tris(3-methoxy-1-propyl) - phosphine)technetium(III)-99m, is a nonreducible complex of Tc(III) which is herein evaluated as a myocardial perfusion imaging agent. METHODS: The biodistribution and dosimetry of 99mTc-Q12 were assessed in 10 normal volunteers, while its potential clinical use was evaluated in 70 patients. RESULTS: Safety parameters measured up to 24 hr postinjection demonstrate no clinically significant drug-related adverse reactions. Technetium(III)-99m-Q12 exhibits good heart uptake (2.2% injected dose at 1 hr postinjection under resting conditions) and no detectable myocardial washout or redistribution up to 5 hr postinjection. The biodistribution is characterized by very rapid hepatobiliary clearance which allows effective myocardial imaging at times as short as 15 min postinjection. Blood and plasma clearances and myocardial uptake are rapid, while lung uptake is minimal. The heart-to-lung and heart-to-liver ratios are higher at stress than at rest, independent of the time elapsed between injection and image acquisition, and independent of whether the patient is fasted or fed after tracer administration. A preliminary correlation shows that 46/47 patients with angiographically demonstrated CAD also have perfusion defects demonstrated by 99mTc-Q12. CONCLUSIONS: On the basis of the studies reported herein, 99mTc-Q12 appears to be a promising myocardial perfusion imaging agent.

Adult↗

Early and delayed brain SPECT with technetium-99m-ECD and iodine-123-IMP in subacute strokes.

UNLABELLED: The brain distribution of 99mTc-ECD versus 123I-IMP was compared in patients with subacute stroke in order to compare diagnostic accuracy. METHODS: A total of 25 patients with subacute stroke underwent early and delayed SPECT imaging with 99mTc-ECD and 123I-IMP. Washout of 99mTc-ECD was calculated and a differential percentage of activity (DPA) of ischemic versus normal zones was assessed. Images were analyzed twice by five independent observers. RESULTS: Technetium-99m-ECD clearance was 12.5% from the whole brain during early imaging. Ischemic parietal zones had higher clearance than normal parietal zones. Technetium-99m-ECD images showed larger differences between abnormal and normal brain activity than 123I-IMP images. Detection accuracy was slightly, but not significantly, higher for 99mTc-ECD and 123I-IMP (sensitivity: 73.8% as 66.6%; specificity: 81.7% as 81.6%). Reproducibility among observers was similar for 99mTc-ECD and early 123I-IMP. CONCLUSION: Technetium-99m-ECD demonstrates high diagnostic accuracy during subacute stroke, similar to 123I-IMP, but with more intense, better delineation of the perfusion defects.

Adult↗

Comparison of technetium-99m-Q3 and thallium-201 for detection of coronary artery disease in humans.

UNLABELLED: Technetium-99m-Q3 is a myocardial imaging agent that produces prompt myocardial visualization in humans. METHODS: In 19 patients with angiographic coronary artery disease, 2 patients with no angiographic coronary artery stenosis greater than 50% of the luminal diameter and 6 healthy volunteers, exercise and resting myocardial imaging were performed with 99mTc-Q3 and also with 201Tl. Technetium-99m-Q3 imaging began 15 min after injection at rest and with exercise, in a complete imaging sequence that required less than 100 min. RESULTS: Overall accuracy for coronary disease detection was 78% (21 true-positive or true-negative studies among 27 study participants) by tomographic thallium imaging versus 89% for 99mTc-Q3 tomographic imaging (p = ns). Accuracy for detection of individual coronary stenoses was 75% (61 true-positive or true-negative coronary segment classifications among 81 total coronary segments) for 201Tl imaging and 83% for 99mTc-Q3 imaging (p = ns). CONCLUSIONS: Technetium-99m-Q3 when used in a rest-exercise sequence that can be completed in 100 min appears to provide comparable diagnostic accuracy to 201Tl for overall coronary disease detection and detection of individual coronary artery stenoses.

Adult↗

Technetium-99m-alendronate: a new radiopharmaceutical for bone scanning.

The purpose of this paper is to report the preparation of a new technetium-99m-radiopharmaceutical for bone scanning. The chelating agent for 99mTc is a new bisphosphonate, alendronate, 4-amino-1-hydroxy-butylidene-1, 1-bisphosphonate (ABP) used as a treatment for osteoporosis. ABP, because of its amino group, seems to be better suited to form a strong and stable complex with technetium-99m and therefore might be better than 99mTc-etidronate (HEDP) or 99mTc-medronate (MDP) for bone scanning. A sterile dry kit containing APB, a reducing agent and a stabilizer was prepared. The parameters studied were molar concentrations, pH, shelf life, labeling efficiency and radiochemical purity. The oven dried sterile kit was formulated with 5 mg ABP, 0.25 mg stannous fluoride and 0.025 mg gentisic acid at pH 2.5-3.5. The labeling efficiency with 20-1500 MBq of pertechnetate (99mTcO4-) was over 95% at room temperature and was stable for 5 h. Technetium-99m-alendronate was tested in two rabbits and it proved to be a promising new radiopharmaceutical for bone scanning. Work is underway to study 99mTc-ABP biodistribution in a statistically significant number of laboratory animals and, later on, to determine radiopharmacokinetic parameters in normal volunteers.

Alendronate↗

Localization of parathyroid glands using technetium-99m-tetrofosmin imaging.

UNLABELLED: Preoperative localization of hyperactive parathyroid glands is useful to minimize operative time and reduce patient morbidity. This investigation compared the sensitivity of radionuclide imaging with 99mTc tetrofosmin with that of ultrasonography and magnetic resonance (MR) imaging in patients with hyperparathyroidism. METHODS: Twenty-six patients with primary (n = 7) or secondary (n = 19) hyperparathyroidism were imaged with 99mTc tetrofosmin, ultrasound and MR imaging of the neck and thorax to localize the lesions. The presence of hyperparathyroidism was identified by an intact parathyroid hormone in vitro assay. The parathyroid/normal thyroid tissue activity ratio was calculated for all patients with evidence of an abnormality on tetrofosmin images. Pathological findings were compared with the results of imaging in 18 of the 26 patients who underwent parathyroidectomy. RESULTS: Technetium-99m tetrofosmin scans demonstrated focal uptake in 46 glands of 26 patients. The uptake was categorized as slight in 78.3% (36/46) and intense (parathyroid/normal thyroid tissue activity ratio, > 1.4) in 21.7% (10/46). Ultrasonography and MR imaging identified 44 and 47 glands, respectively, in these patients. Eleven of the 18 patients who underwent parathyroidectomy within 1 mo after tetrofosmin imaging had hyperplastic glands, while 7 had parathyroid adenomas. Tetrofosmin imaging successfully localized 7 of 7 (100%) adenomas and 27 of 37 (73.0%) hyperplastic glands. The sensitivities of each technique for localizing abnormal parathyroid glands were 77.3% (34/44) for tetrofosmin imaging: 68.2% (20/44) for ultrasonography: and 68.2% (30/44) for MR imaging. Technetium-99m tetrofosmin uptake ratio in the 18 patients with surgical exploration was not proportional to several oxyphil cells. CONCLUSION: Technetium-99m tetrofosmin parathyroid imaging may be useful for localizing abnormal glands in patients with primary and secondary hyperparathyroidism. The sensitivity of 99mTc tetrofosmin parathyroid imaging was high as compared to ultrasonography or MR imaging. The prolonged retention of tetrofosmin may not depend on the number of mitochondria-rich oxyphil cells.

Adenoma↗

Technetium-99m-labeled HL91 to identify tumor hypoxia: correlation with fluorine-18-FDG.

UNLABELLED: Technetium-99m HL91 is a potential agent for imaging hypoxic tissue in vivo. A pilot evaluation using a prototype formulation assessed efficacy in tumor imaging and compared results with 18F-fluorodeoxyglucose (FDG) PET. METHODS: Ten patients with malignant tumors were included. Tumors included carcinoma of the bronchus (n = 3), carcinoma of the thyroid (n = 2), lymphoma (n = 2), soft tissue sarcoma (n = 1), carcinoid (n = 1) and carcinoma of the breast (n = 1). Whole-body planar scans and localized SPECT scans were performed at 1 and 4 hr postinjection of 600 MBq 99mTc HL91. Half-body and localized emission/transmission 18F-FDG PET scans were performed 60 min postinjection 370 MBq 18F-FDG in eight patients. Lesion-to-normal tissue background ratios were measured for all 99mTc HL91 and 18F-FDG PET scans and percentage uptake and standardized uptake values measured for 99mTc HL91 and 18F-FDG PET, respectively. RESULTS: Technetium-99m HL91 showed visible uptake into the tumor area in all seven studies where the tumor was clearly identified by 18F-FDG PET; 99mTc HL91 uptake was not detected in one study (carcinoid) in which 18F-FDG was weakly positive. Two further tumors, in which PET correlation was not available, showed accumulation of 99mTc HL91. In two 99mTc HL91 studies, abnormality was apparent only on SPECT images. Lesion-to-normal tissue background ratios for 99mTc HL91 ranged from 1.22/2.53 at 1 hr and 1.33/2.89 at 4 hr on planar images and 1.23/5.2 and 1.67/14.6 on SPECT images, respectively. CONCLUSION: In this study, the use of 99mTc HL91 resulted in uptake in the majority of malignant tumors identified by 18F-FDG-PET. Technetium-99m HL91 exhibits good imaging characteristics, with imaging at 4 hr providing good lesion-to-normal tissue background ratios, that are further enhanced by SPECT.

Aged↗

Technetium Tc 99m diphosphonate bone scan. False-normal findings in elderly patients with hematogenous vertebral osteomyelitis.

Hematogenous osteomyelitis is usually diagnosed by an abnormal technetium Tc 99m diphosphonate bone scan in symptomatic patients who have positive blood cultures. False-normal 99mTc bone scans have been described recently in neonates with biopsy-proved osteomyelitis. This phenomenon seems to be extremely rare in adults. Two elderly patients with hematogenous vertebral osteomyelitis had normal technetium Tc 99m diphosphonate bone scans when first evaluated. In both cases the bone scans became abnormal four to six weeks after onset of symptoms and two to four weeks after the initial normal results of the study. When suggested by the clinical picture, hematogenous osteomyelitis cannot be ruled out by a normal 99mTc bone scan at any age. Gallium scan, computed tomographic scan, or bone biopsy can be helpful in such cases.

Aged↗

Blood flow imaging of a posterior circulation stroke. Use of technetium Tc 99m hexamethylpropyleneamine oxime and single photon emission computed tomography.

Regional cerebellar perfusion was imaged using technetium Tc 99m hexamethylpropylene amine oxime and single photon emission computed tomography (HM-PAO-SPECT) in a patient with chronic left lateral medullary syndrome with contralateral weakness due to traumatically induced thrombosis of the left vertebral artery. Despite continued neurologic deficits, x-ray transmission computed tomography was normal. However, HM-PAO-SPECT demonstrated that blood flow to the left cerebellar hemisphere was significantly impaired. This abnormality was still apparent after correction for atrophy as estimated by magnetic resonance imaging. Technetium Tc 99m hexamethyl-propyleneamine oxime and single photon emission computed tomography effectively imaged regional blood flow in the vertebrobasilar circulation and appears to more clearly reflect the nature and extent of the neurologic deficit than either x-ray transmission computed tomography or magnetic resonance scanning.

Cerebrovascular Circulation↗

Radionuclide lymphoscintigraphy with technetium 99m antimony sulfide colloid to identify lymphatic drainage of cutaneous melanoma at ambiguous sites in the head and neck and trunk.

Frequently the primary lesion of high-risk cutaneous melanoma (level III, greater than or equal to 1.5mm; greater than or equal to 1.0 mm with ulceration) is in an ambiguous lymphatic drainage site on the trunk, pelvic and shoulder girdles, and head and neck area. Lymphoscintigrams were performed by a circumferential intradermal injection of the biopsy site using technetium 99m (99mTc) antimony sulfide colloid in a total dose of 0.2 to 0.6 mCi in a volume of 0.1 to 0.5 ml. Imaging was done with a large-field gamma camera with high-resolution parallel hole collimator. Technetium 99m antimony sulfide colloid is an ideal agent for lymphoscintigrams because of small particle size (3-30 micron), which permits early migration into the interstitial space and lymphatics and rapid pickup by lymph nodes. Although it is a gamma emmitter with high activity, it has a short half-life and does not induce tissue necrosis. It does not localize the site of lymph node metastases, but indicates only the drainage pattern. Images were obtained at 1, 5, 10, 15, 30, and 60 minutes, respectively, and then three times every hour. Surgery was usually performed 24 hours later. The majority of patients had lesions with ambiguous drainage sites: head and neck (4 of 5 patients) and trunk (9 of 13 patients). The drainage by scan was to unpredictive sites in 72%, and resulted in a change of treatment planning by location and extent of ablation with node dissection in 9 of 18 patients. Ambiguous dissection sites included: (1) question of preauricular dissection with parotidectomy versus posterior auricular and cervical dissection for selected scalp lesions; (2) low-neck with or without axillary dissection for upper chest and shoulder lesions; and (3) axillary versus groin dissections for midflank lesions at zone of ambiguity between axilla and groin. It was concluded that preoperative 99mTc antimony sulfide lymphoscintigraphy is a highly useful planning technique in determining the appropriate lymphatic drainage basin for dissection in selected melanoma patients.

Adult↗

Sequential technetium-99m/gallium-67 scintigraphic evaluation of subclinical osteomyelitis complicating fracture nonunion.

Twenty-four patients with a history of post-traumatic fracture nonunion underwent sequential 99mTc and 67Ga citrate scintigraphy in an attempt to differentiate between posttraumatic fracture nonunion and nonunion complicated by subclinical osteomyelitis. Neither technetium nor gallium studies alone nor in combination, with or without clinical correlation, could help delineate between fracture nonunion and nonunion complicated by subclinical osteomyelitis because of the increased technetium and gallium radioisotope uptake associated with the nonunion site.

Adolescent↗

Extravascular chest wall technetium 99m diethylene triamine penta-acetic acid: implications for the measurement of renal function during renography.

Measurement of individual kidney glomerular filtration rate (IKGFR) from the gamma-camera technetium 99m diethylene triamine penta-acetic acid (99mTc-DTPA) renogram requires a continuous measurement of arterial activity. This is usually based on a region of interest (ROI) placed over the cardiac blood pool on the posterior view, with the assumption of negligible contamination from activity in the extravascular space of the chest wall. By injecting a small dose of technetium 99m human serum albumin (HSA) before the 99mTc-DTPA in 12 patients undergoing routine renography, the contribution of extravascular activity to the total signal recorded over the cardiac blood pool was calculated to be 11.0% (SE 2.1%) 1.5 min after DTPA injection, rising to 35.1% (SE 2.5%) at 15 min. Subtraction of the time-activity curve recorded from a ROI of the same size over the right lung generated a "pure" blood signal as shown by almost identical HSA/DTPA signal ratios recorded in blood samples taken 5 min after HSA and 15 min after DTPA and from the gamma-camera at the corresponding times. The effect of using a cardiac blood pool time-activity curve uncorrected for extravascular activity was to overestimate IKGFR by an average factor of 1.17 (SE 0.03).

Glomerular Filtration Rate↗

Assessment of ventricular function with first-pass radionuclide angiography using technetium 99m hexakis-2-methoxyisobutylisonitrile: a European multicentre study.

In the context of a multicentre study on the use of technetium 99m hexakis-2-methoxyisobutylisonitrile (99mTc-Sestamibi), we evaluated the accuracy of the ventricular function assessed at rest by means of first-pass radionuclide angiocardiography acquired during the injection of the tracer for myocardial perfusion scintigraphy. The results were compared with first-pass studies performed using reference tracers sodium pertechnetate Tc 99m or technetium 99m diethylene triamine penta-acetic acid or with gated radionuclide angiocardiography. A total of 66 patients of the 105 enrolled in the study could be evaluated. The comparison of the first-pass studies was possible in 33 subjects with regard to the left ventricular ejection fraction, yielding r = 0.909 (P less than 10(-6)), and in 22 cases with regard to the right ventricular ejection fraction, yielding r = 0.712 (P less than 0.001). The comparison between the first-pass study using 99mTc-Sestamibi and the equilibrium gated radionuclide angiocardiography was possible for the left ventricular ejection fraction in 26 cases, with r = 0.937 (P less than 10(-6)), and for the right ventricular ejection fraction in 15 subjects, with r = 0.783 (P less than 0.001). In conclusion, the assessment of ventricular function performed by acquiring a first-pass radionuclide angiocardiograph during the injection of 99mTc-Sestamibi for perfusion myocardial scintigraphy can be considered reliable and accurate, when compared with the usually employed techniques. This result confirms the feasibility of a combined evaluation of perfusion and function at rest and during stress testing, which represents one of the most interesting advantages offered by the use of 99mTc-Sestamibi.

Coronary Disease↗

Spontaneous perforation of the ureter diagnosed on technetium 99m DTPA excretory urography.

A case of nontraumatic rupture of the ureter secondary to a nonopaque calculus is presented. Because of the inherent high image contrast caused by the leak of technetium 99m-DTPA-labeled urine, the technetium 99m-DTPA excretory urogram is seen as an alternative to the intravenous urogram or contrast-enhanced computed tomography in selected cases of suspected ureteral rupture.

Humans↗

Increased incidence and clinical correlation of persistently abnormal technetium pyrophosphate myocardial scintigrams following acute myocardial infarction in patients with diabetes mellitus.

"Persistently abnormal" technetium-99m stannous pyrophosphate myocardial scintigrams (PPi+) appear to be associated with a relatively poor prognosis after acute myocardial infarction (AMI). To assess the incidence and implications of PPi+, we performed a retrospective analysis in 29 patients with and 25 patients without diabetes mellitus who had abnormal myocardial scintigrams within 4 days of AMI and who had follow-up scintigrams at least 3 months after hospital discharge. There were no significant differences between patients with and without diabetes as regards age, incidence of transmural or nontransmural AMI, or degree of left ventricular dysfunction after AMI. Persistently abnormal PPi+ occurred more commonly in patients with diabetes than in nondiabetic patients (18 of 29, 62%, compared to 3 of 25, 12%; p less than 0.001). Patients with chronic PPi+ had more frequent cardiac complications following hospital discharge (p less than 0.005) including death, recurrent AMI, unstable angina, and intractable congestive heart failure. Postmortem analysis in two patients with diabetes and chronic PPi+ revealed marked myocytolysis. Thus, patients with diabetes mellitus have an increased incidence of post-AMI "persistently abnormal" technetium (PPi+) scintigrams and relatively poor prognosis following myocardial infarction.

Aged↗

Early estimation of acute myocardial infarct size soon after coronary reperfusion using emission computed tomography with technetium-99m pyrophosphate.

Early appearance of positive findings on a technetium-99m pyrophosphate scan has been shown to be associated with the presence of a reperfused acute myocardial infarction (AMI). Early technetium-99m pyrophosphate imaging was performed by emission computed tomography to evaluate reperfusion and to test the feasibility of estimating infarct size soon after coronary reperfusion based on acute positive tomographic findings. Twenty-seven patients with transmural AMI who were treated with intracoronary urokinase infusion followed by percutaneous transluminal coronary angioplasty underwent pyrophosphate imaging 8.7 +/- 2.1 hours after the onset of AMI. None of the 8 patients in whom reperfusion was unsuccessful had acute positive findings. Of 19 patients in whom reperfusion was successful, 17 had acute positive findings (p less than 0.001). In these 17, tomographic infarct volumes were determined from reconstructed transaxial images. The threshold for areas of increased pyrophosphate uptake within the infarct was set at 60% of peak activity by the computerized edge-detection algorithm. The total number of pixels in all transaxial sections showing increased tracer uptake were added and multiplied by a size factor and 1.05 g/cm3 muscle to determine infarct volume. The correlations of tomographic infarct volumes with peak serum creatine kinase (CK) levels (r = 0.82) and with cumulative release of CK-MB isoenzyme (r = 0.89) were good. Moreover, the time to positive imaging was significantly shorter than that to peak CK level (8.5 +/- 2.3 vs 10.4 +/- 2.2 hours, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Use of technetium-99m isonitrile (RP-30A) in assessing left ventricular perfusion and function at rest and during exercise in coronary artery disease, and comparison with coronary arteriography and exercise thallium-201 SPECT imaging.

This study compared the results of stress and rest single-photon emission computed tomography imaging of myocardial perfusion using technetium-99m isonitrile (RP-30A) with the results of stress and redistribution tomographic thallium imaging and the results of coronary arteriography in 39 patients, 11 without and 28 with coronary artery disease (CAD). Each patient underwent 2 exercise studies at identical workload, heart rate and double product. In a subset of 13 patients, concomitant evaluation of left ventricular (LV) function using first-pass radionuclide angiography with a multi-crystal camera also was performed with bolus injections of isonitrile. Isonitrile had similar sensitivity (82 vs 82%, difference not significant), a slightly--but not significantly--higher specificity (100 vs 82%) and similar predictive accuracy (87 vs 82%) to thallium-201. The tracer uptake was assessed in 20 segments/study. There was concordance between the isonitrile and thallium-201 images in 723 of the 780 segments (93%) (kappa = 0.83 +/- 0.02). In general, the isonitrile images were considered of better quality than the thallium-201 images. All 10 patients with CAD who underwent concomitant first-pass radionuclide angiography had either perfusion abnormalities or an abnormal ejection fraction response to exercise. Thus, technetium-99m isonitrile provides a reliable method of assessment of CAD with a sensitivity, specificity and predictive accuracy comparable to that of exercise thallium-201 imaging. Additional advantages include better image quality and the ability to obtain concomitant assessment of LV function with the use of first-pass radionuclide angiography.

Angiography↗

Technetium-99m HIDA hepatobiliary scanning in evaluation of afferent loop syndrome.

A study of 118 patients, operated on with Billroth II gastrectomy for peptic disease and affected by postgastrectomy syndromes, was carried out. Fifty patients were investigated by means of technetium-99m HIDA hepatobiliary scanning. In 18 patients, in whom an afferent loop syndrome was clinically suspected, hepatobiliary scanning demonstrated an altered afferent loop emptying in 8 and atonic distension of the gallbladder without afferent loop motility changes in 10. Among the patients in the first group, four were treated with a biliary diversion surgical procedure and in the second group, two patients underwent cholecystectomy. Our findings indicate that biliary vomiting, right upper abdominal pain pyrosis, and biliary diarrhea in Billroth II gastrectomized patients are not always pathognomonic symptoms of afferent loop syndrome. Technetium-99m HIDA hepatobiliary scanning represents the only diagnostic means of afferent loop syndrome definition. A differential diagnosis of abnormal afferent loop emptying and gallbladder dyskinesia is necessary for the management planning of these patients, and furthermore, when a surgical treatment is required, biliary diversion with Roux-Y anastomosis or Braun's biliary diversion seems the treatment of choice for afferent loop syndrome, whereas cholecystectomy represents the best procedure for atonic distension of the gallbladder.

Adult↗