Dobutamine-atropine stress echocardiography and dipyridamole sestamibi scintigraphy for the detection of coronary artery disease: limitations and concordance.

OBJECTIVES: We sought to compare dobutamine-atropine stress echocardiography (DASE) and dipyridamole Technetium 99-m (Tc-99m) sestamibi single photon emission computed tomography (SPECT) scintigraphy (DMIBI) for detecting coronary artery disease (CAD). BACKGROUND: Both DASE and DMIBI are effective for evaluating patients for CAD, but their concordance and limitations have not been directly compared. METHODS: To investigate these aims, patients underwent multistage DASE, DMIBI and coronary angiography within three months. Dobutamine-atropine stress echocardiography and stress-rest DMIBI were performed according to standard techniques and analyzed for their accuracy in predicting the extent of CAD. Segments were assigned to vascular territories according to standard models. Angiography was performed using the Judkin's technique. RESULTS: The 183 patients (mean age: 60 +/- 11 years, including 50 women) consisted of 64 patients with no coronary disease and 61 with single-, 40 with two- and 18 with three-vessel coronary disease. Dobutamine-atropine stress echocardiography and DMIBI were similarly sensitive (87%, 104/119 and 80%, 95/119, respectively) for the detection of CAD, but DASE was more specific (91%, 58/64 vs. 73%, 47/64, p < 0.01). Sensitivity was similar for the detection of CAD in patients with single-vessel disease (84%, 51/61 vs. 74%, 45/61, respectively) and multivessel disease (91%, 53/58 vs. 86%, 50/58, respectively). Multiple wall motion abnormalities and perfusion defects were similarly sensitive for multivessel disease (72%, 42/58 vs. 66%, 38/53, respectively), but, again, DASE was more specific than DMIBI (95%, 119/125 vs. 76%, 95/125, respectively, p < 0.01). Dobutamine-atropine stress echocardiography and DMIBI were moderately concordant for the detection and extent of CAD (Kappa 0.47, p < 0.0001) but were only fairly (Kappa 0.35, p < 0.001) concordant for the type of abnormalities (normal, fixed, ischemia or mixed). CONCLUSIONS: Dobutamine-atropine stress echocardiography and DMIBI were comparable tests for the detection of CAD. Both were very sensitive for the detection of CAD and moderately sensitive for the extent of disease. The only advantage of DASE was greater specificity, especially for multivessel disease. Dobutamine-atropine stress echocardiography may be advantageous in patients with lower probabilities of CAD.

Biodistribution of 99Tcm-labelled 5-thio-D-glucose.

We studied the biodistribution and tumour localization of 99Tcm-labelled-5-thio-D-glucose (99Tcm-TG). 5-Thio-D-glucose was labelled with 99Tcm by direct stannous ion reduction. The biodistribution of 99Tcm-TG was investigated in normal rabbits and in mice bearing experimental tumours. In rabbits, the plasma and clearance of 99Tcm-TG was 14.5 +/- 2.0 and 11.3 +/- 3.0 ml.min-1 respectively. Urinary excretion at 1 h was 53 +/- 5%. 99Tcm-TG was injected intravenously in mice bearing MC26 colon carcinoma and tissue samples were analysed by gamma scintillation counting at various times. Uptake of 99Tcm-TG in tumour at 1 and 3 h was 1.6 +/- 0.3% and 1.2 +/- 0.3%; the tumour to muscle ratios were 2.7:1 and 4:1 respectively. The autoradiographic biodistribution of 99Tcm-TG in MX-1 human breast xenografted nude mice showed more persistent tumour uptake of 99Tcm-TG than 14C-2-deoxyglucose (14C-DG). 99Tcm-TG accumulated in the centre of the tumours; 14C-DG was decreased in this central region probably because of zones of infarction on necrosis. The discordance between the tumour uptake of 99Tcm-TG and 14C-DG indicates that 99Tcm-TG does not act like a glucose analog, suggesting 99Tcm-TG avidity for zones of infarction or necrosis. The further study of 99Tcm-TG in tumours and ischaemic injury is warranted.

Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Detection of osteomyelitis in the neuropathic foot: nuclear medicine, MRI and conventional radiography.

The diagnostic efficacy of (1) combined three-phase bone scintigraphy and In-111 labeled WBC scintigraphy (Bone/WBC), (2) MRI, and (3) conventional radiography in detecting osteomyelitis of the neuropathic foot was compared. Conventional radiography was comparable to MRI for detection of osteomyelitis. MRI best depicted the presence of osteomyelitis in the forefoot. Particularly in the setting of Charcot joints, Bone/WBC was more specific than conventional radiography or MRI.

SPET and three-phase planar bone scintigraphy in adult patients with chronic low back pain.

Among adults, low back pain (LBP) persisting for more than 3 months is a common complaint. A variety of imaging modalities including bone scintigraphy have been recommended as appropriate for the investigation of chronic LBP, even when there is no reason to suspect that the pain is due to tumour, infection or inflammatory arthritis. In this chronic LBP population, the diagnostic benefit of bone SPET, together with planar flow study, blood pool and delayed three-phase imaging, was assessed, Altogether, 2108 consecutive adult patients were entered into the chronic LBP bone scintigraphy database. Retrospective exclusion of patients with a history of tumour, infection or inflammatory arthritis reduced the population to 1390, of whom 916 underwent a lumbosacral spine flow study and blood pool imaging in addition to planar and SPET bone scintigraphy. The diagnostic benefit of these imaging studies was tabulated and compared. In addition, a retrospective chart review of the patients with renal and other soft tissue abnormalities identified by a flow study and blood pool imaging was undertaken with a view to documenting any changes in treatment planning over the 6 months following the nuclear medicine studies. Of the lumbosacral spine abnormalities, 44.1% were seen equally well on planar and SPET images, 24.0% better on SPET, 31.4% only seen on SPET, and 0.4% only seen on planar imaging. The distribution of abnormalities identified on SPET images in the lumbar spine was divided between vertebral bodies (36.1%), lamina or pedicles (which included frequent sites of increased uptake in the articular facets and pars interarticularis) (53.8%), spinous processes (8.7%) and transverse processes (1.3%). For the flow study and blood pool imaging, there was a 16.7% rate of positive studies. However, there were no documented changes in treatment planning because of these positive findings. In conclusion, when used to examine adult patients with chronic LBP, SPET detects significantly more scintigraphic abnormalities than planar imaging. The addition of a flow study and blood pool imaging as part of these LBP examinations results in a significant benefit. However, the clinical utility of such flow study and blood pool imaging studies cannot be confirmed.

Low dose dobutamine echocardiography is more predictive of reversible dysfunction after acute myocardial infarction than resting single photon emission computed tomographic thallium-201 scintigraphy.

To directly compare dobutamine echocardiography and resting single photon emission computed tomographic (SPECT) thallium-201 (Tl-201) scintigraphy for the detection of reversible dysfunction, 64 patients underwent dobutomine echocardiography (baseline, low dose 5 and 10 mg/kg/min, and peak dose), rest Tl-201 scintigraphy (3 mCi - 15 minute and 3- to 4-hour SPECT imaging), and coronary angiography during the first week after acute myocardial infarction. Follow-up echocardiography was performed 4 to 8 weeks after discharge. Wall thickening improved at follow-up in 52% (207 of 399) of the dysfunctional segments. By receiver operating characteristic analysis, biphasic responses and sustained improvement during dobutamine echocardiography were more accurate (p < 0.01) than Tl-201 uptake by SPECT scintigraphy for reversible dysfunction. The greater accuracy of dobutamine echocardiography resulted from higher accuracy in akinetic segments, Q wave infarction, and multivessel coronary artery disease. In conclusion, dobutamine echocardiography was more accurate than resting SPECT Tl-201 scintigraphy for reversible dysfunction after acute myocardial infarction.

Evaluation of 99Tcm-bicisate as a renal imaging agent.

99Tcm-bicisate (99Tcm-ECD), often used as a brain perfusion agent, is rapidly converted following intravenous injection to the polar monoacid (99Tcm-ECM) and diacid (99Tcm-EC) metabolites. Such polar metabolites, which are eliminated principally by renal clearance, are potential renal imaging agents. In this study, 99Tcm-ECD was compared for the first time with 99Tcm-EC, 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) and 131I-orthoiodohippurate (OIH) as renal imaging agents in rabbits. Whole-body images and renograms were obtained for all three of the 99Tcm agents, and pharmacokinetic parameters including plasma and urinary clearance were studied for all four agents. The plasma clearance of 99Tcm-EC (37 ml min-1) was slower than that of 99Tcm-ECD (51 ml min-1), which could be accounted for by the higher liver uptake of 99Tcm-ECD. The urinary clearance of 99Tcm-ECD (35 ml min-1), 99Tcm-EC (34 ml min-1) and 99Tcm-MAG3 (39 ml min-1) was similar. The renal images obtained with 99Tcm-ECD were comparable to those for 99Tcm-MAG3 and 99Tcm-EC. However, liver uptake was more prominent with 99Tcm-ECD than with the other agents. The 99Tcm-ECD renogram curves showed a prolonged decrease in renal activity compared to both 99Tcm-EC and 99Tcm-MAG3. In potential human studies, the relatively high liver uptake of 99Tcm-ECD superimposed on right renal activity may be a limitation. Therefore, we conclude that 99Tcm-ECD is less favourable when compared to existing renal agents due to its high extrarenal uptake and renal kinetics.

Evaluation of 99Tc(m)-ECD as a white blood cell labelling agent.

99Tc(m)-ECD is a new agent for perfusion brain imaging. Its brain retention is attributed to the enzymatic conversion of lipophilic 99Tc(m)-ECD to polar monoacid and diacid derivatives. Based on its proposed mechanism of retention in the brain, labelling of white blood cells (WBC) with 99Tc(m)-ECD has been studied at our laboratory. A labelling efficiency of 42% was achieved by incubating WBC with 99Tc(m)-ECD in phosphate buffered saline medium for 30 min. There was a washout of 50% of the radioactivity from the cells in 1 h, which might contribute to increased background in potential human studies. However, rapid urinary elimination of the radioactivity is expected to deal with this problem due to the rapid in vivo conversion of the parent compound to polar metabolites. 99Tc(m)-ECD appears to be a promising agent for labelling WBC. Furthermore, already prepared multidose 99Tc(m)-ECD may be used for either brain perfusion imaging or WBC labelling.

Diagnostic bone scanning in oncology.

Over the last several decades bone scanning has been used extensively in the evaluation of oncology patients to detect bone involvement. It can provide information about disease location, prognosis, and the effect of therapy. Bone scanning offers the advantages of whole body evaluation and the detection of lesions earlier than other techniques. However, as newer diagnostic tools become available, indications for bone scanning must be revised and the results combined with these other tests in order to provide optimum patient care. Advances in instrumentation and the subsequent improvement in image quality have allowed nuclear medicine physicians to provide more accurate bone scan interpretations. By optimizing image acquisition, it is often possible to determine lesion characteristics, which are more likely to represent malignancy. Knowledge of disease pathophysiology and other specific properties of the patient's primary tumor, along with subsequent correlation of scan abnormalities to patient history, physical examination, previous studies, and other radiological examinations, is essential for determining lesion significance. The differential diagnosis of a scan abnormality should also include consideration of both false normal and abnormal causes. The final interpretation should be clearly communicated to the clinician with appropriate recommendations for further evaluation. Only through careful attention to the patient, the clinician, and appropriate study acquisition parameters will bone scanning maintain its place in the evaluation of oncology patients.

Effect of gallium nitrate therapy on Ga-67 scintigraphic detection of lymphoma: case report.

Ga-67 and abdominal CT scans of a 72-year-old woman who had malignant lymphoma before, during, and after gallium nitrate/hydroxyurea combination therapy are presented. Disappearance of Ga-67 uptake by the tumor during this treatment despite continuing CT evidence of disease and reappearance of Ga-67 scan abnormalities after cessation of therapy suggests that caution should be exercised when interpreting results of Ga-67 scintigraphy for the detection of tumor viability during gallium nitrate/hydroxyurea therapy.

Enterogastric bile reflux during technetium-99m-sestamibi cardiac imaging.

UNLABELLED: Enterogastric bile reflux (EGBR), a risk factor for both gastritis and esophagitis, is a potentially treatable noncoronary cause for chest pain. METHODS: To investigate the frequency of EGBR during different 99mTc-sestamibi cardiac imaging, 1405 consecutive 99mTc-sestamibi SPECT myocardial perfusion studies were reviewed. RESULTS: One hundred sixteen of the 1405 patient studies (8.3%) showed EGBR with roughly equal numbers of patients having marked (43 patients), moderate (38 patients) or minimal (35 patients) intensity of abnormal gastric activity. Two examinations showed gastroesophageal reflux of activity. EGBR was less frequent with treadmill stress testing (5.5% patients) than with pharmacologic stress testing using either dipyridamole (11% of patients) or dobutamine (9.2% of patients) (p > 0.005). EGBR also was more frequent in patients over 40 yr of age. Finally, the prevalence of upper gastrointestinal symptoms and the frequency of established upper gastrointestinal diagnoses correlated strongly with the presence and intensity of EGBR. CONCLUSION: Clarification of the full clinical significance of EGBR during 99mTc-sestamibi cardiac imaging is a topic for future research. Nonetheless, the imaging finding of EGBR may, in fact, identify a potentially treatable noncoronary cause for chest pain.

A high-efficiency, rapid and multi-dose procedure for white blood cell labelling with 99Tcm-HMPAO.

99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) is presently recognized as an effective radiopharmaceutical for in vitro white blood cell (WBC) labelling in addition to its widespread utility in cerebral blood flow imaging. While performing clinical studies in patients with a wide range of inflammatory diseases, the effect of the ligand and stannous ion quantity on the labelling efficiency (LE) of WBC was examined. A mean LE of 64 +/- 7% (n = 29) was achieved when the whole HMPAO kit was used for labelling. The LEs were 78 +/- 5% (n = 43), 83 +/- 3% (n = 37) and 85 +/- 5% (n = 18) when one-half, one-third and one-fifth of the lyophilized kit was used, respectively. This is in agreement with the reports of Sampson et al. and Lang et al., suggesting that the optimal formulation of the 99Tcm-HMPAO is a faction of the whole kit. Accordingly, fractionation of a freshly prepared 99Tcm-HMPAO kit into five parts for a high-efficiency WBC labelling is proposed, encouraging the more widespread use of 99Tcm-HMPAO in WBC labelling.

In-111 WBC imaging of osteomyelitis in patients with underlying bone scan abnormalities.

One hundred seven combined In-111 WBC/Tc-99m MDP scans performed on 87 patients with a high clinical suspicion of osteomyelitis were retrospectively reviewed. An 86% sensitivity and a 94% specificity for detecting osteomyelitis were found. In addition, patients were grouped into one of five clinical settings for more detailed analysis: diabetic osteoarthropathy, previous arthroplasty, fracture, overlying skin ulcer, and other etiology. Forty-seven studies were performed while patients received antibiotic therapy without loss of sensitivity for detecting osteomyelitis. Results obtained with scintigraphy compared favorably to other imaging and laboratory studies used to detect osteomyelitis. In conclusion, the combined In-111 WBC/Tc-99m MDP scan is a very sensitive and specific method to detect osteomyelitis in patients with concurrent diabetic osteoarthropathy, fracture, postoperative healing, and overlying skin ulcer. Antibiotic treatment does not appear to adversely affect the sensitivity of these scans.

Prospective study of bone, indium-111-labeled white blood cell, and gallium-67 scanning for the evaluation of osteomyelitis in the diabetic foot.

Twenty-two adult diabetic patients with clinical suspicion of foot and/or ankle infection were prospectively evaluated using radiography, technetium-99m methylene diphosphonate bone scanning (99mTc), indium-111-labeled leukocyte scanning (111In), and gallium-67 scanning (67Ga) to determine the presence of clinically suspected osteomyelitis. Biopsy for culture and histology was performed in 16 patients. The diagnosis of osteomyelitis was confirmed by biopsy in 12 patients. The remaining 10 patients had no evidence of osteomyelitis with long-term follow-up. 99mTc was shown to be of limited valued when used alone in these patients with peripheral neuropathy. 67Ga, either alone or in combination with 99mTc bone scanning, was of little diagnostic value and gave no additional information that was not available from 111In. The combination of three-phase 99mTc and 111In had the highest diagnostic efficacy (100% sensitivity, 80% specificity, and 91% accuracy), followed closely by 111In alone (100% sensitivity, 70% specificity, and 86% accuracy). We conclude that for adult diabetic patients with clinical suspicion of osteomyelitis but no radiographic findings of that disease, 111In alone is an appropriate nuclear medicine evaluation for ruling out infection if it is negative. However, if an area of 111In white blood cell uptake is present, a "simultaneous" 99mTc is often helpful in providing the anatomic correlation to differentiate osteomyelitis from infection that is limited to soft tissue.

Detection of pulmonary embolism in patients with unresolved clinical and scintigraphic diagnosis: helical CT versus angiography.

OBJECTIVE: This study was designed to prospectively compare helical CT with pulmonary angiography in the detection of pulmonary embolism in patients with an unresolved clinical and scintigraphic diagnosis. SUBJECTS AND METHODS: Twenty patients with an unresolved suspicion of pulmonary embolism were evaluated with contrast-enhanced helical CT and with selective pulmonary angiography. An average of 11 hr separated the two studies. The CT scans were obtained during one 24-sec or two 12-sec breath-holds. CT scans were interpreted without knowledge of the results of scintigraphy or angiography. Selective pulmonary angiograms were obtained with knowledge of the findings on the ventilation/perfusion scan only. The sensitivity and specificity of CT were compared with those of angiography for central vessels (segmental and larger) only and for all vessels. RESULTS: Eleven of the 20 patients had proved pulmonary embolism (seven in central vessels and four in subsegmental vessels only). When only central vessels were analyzed, CT sensitivity was 86%, specificity was 92%, and the likelihood ratio was 10.7. However, when subsegmental vessels were included, CT results were 63%, 89%, and 5.7, respectively. CONCLUSION: In our subset of patients, helical CT was only 63% sensitive. Subsegmental emboli are difficult to diagnose. Pulmonary angiography remains the study of choice. CT has a limited role in the evaluation of acute pulmonary embolism.

Evaluation of regional cerebral blood flow in massive intracerebral calcifications.

Fahr's disease is histopathologically characterized by massive bilateral calcifications of the cerebral basal ganglia, the dentate nuclei of the cerebellum and both the cerebral and cerebellar cortices. We report a case of Fahr's disease in which a 99mTc-hexamethyl-propylenamine oxime (99mTc-HMPAO) brain SPECT study was used to evaluate regional cerebral blood flow to the calcified regions. There was markedly decreased perfusion to the basal ganglia bilaterally as well as decreased perfusion to the cerebral cortices that correlated well with the patient's clinical condition.