Assessment of myocardial washout of Tc-99m-sestamibi in patients with chronic heart failure: comparison with normal control

BACKGROUND: In contrast to 201TlCl, 99mTc-sestamibi shows very slow myocardial clearance after its initial myocardial uptake. In the present study, myocardial washout of 99mTc-sestamibi was calculated in patients with non-ischemic chronic heart failure (CHF) and compared with biventricular parameters obtained from first-pass and ECG-gated myocardial perfusion SPECT data. METHODS AND RESULTS: After administration of 99mTc-sestamibi, 25 patients with CHF and 8 normal controls (NC) were examined by ECG-gated myocardial perfusion SPECT and planar data acquisition in the early and delayed (interval of 3 hours) phase. Left ventricular ejection fraction (LVEF, %), peak filling rate (PFR, sec(-1)), end-diastolic volume (LVEDV, ml) and end-systolic volume (LVESV, ml) were automatically calculated from the ECG-gated SPECT data. Myocardial washout rates over 3 hours were calculated from the early and delayed planar images. Myocardial washout rates in the CHF group (39.6+/-5.2%) were significantly higher than those in the NC group (31.2+/-5.5%, p < 0.01). The myocardial washout rates for the 33 subjects showed significant correlations with LVEF (r = -0.61, p < 0.001), PFR (r = -0.47, p < 0.01), LVEDV (r = 0.45, p < 0.01) and LVESV (r = 0.48, p < 0.01). CONCLUSION: The myocardial washout rate of 99Tc-sestamibi is considered to be a novel marker for the diagnosis of myocardial damage in patients with chronic heart failure.     

The effect of chemotherapy on the uptake of technetium-99m sestamibi in breast cancer

Technetium-99m sestamibi scintimammography has been used primarily in the diagnosis of breast cancer. It has also been suggested that this technique could be used to monitor response to chemotherapy and possibly to predict those patients in whom no response can be expected. An initial study was performed in nine patients with primary breast cancer. All patients underwent prone lateral and anterior^99mTc-sestamibi imaging at diagnosis and 4–7 months later, after they had received cytotoxic chemotherapy. The uptake of^99mTc-sestamibi in the breast was compared with that in normal surrounding breast tissue and this ratio was expressed as the target to background ratio. In all patients treated there was a reduction in uptake of^99mTc-sestamibi after treatment, such that whilst all the tumours could be seen before treatment, only three were visible following chemotherapy. There was a significant fall in the mean target to background ratio of the patients undergoing chemotherapy: the tumour to background ratio was 2.48 before chemotherapy and 1.40 after treatment (P<0.001, paired Student'st test). This fall in tumour activity was observed both in those patients in whom a clinical response was seen and in the two patients in whom the tumour enlarged despite chemotherapy. It appears that the reduced uptake of^99mTc-sestamibi seen after chemotherapy may be a non-specific change and therefore may not be predictive of the clinical response to treatment.     

Simultaneous assessment of Tc-99m-sestamibi and I-123-BMIPP myocardial distribution in patients with myocardial infarction: Evaluation of left ventricular function with ECG-gated myocardial SPECT

123I-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) is a branched-chain free fatty acid that is used to evaluate various cardiac diseases. The aim of the present study was to investigate the relationship between myocardial perfusion (99mTc-sestamibi) and BMIPP uptake, and to correlate perfusion and metabolic alterations with regional left ventricular dysfunction in patients with myocardial infarction (MI). ECG-gated dual-isotope myocardial SPECT was performed on 130 patients with MI with sestamibi (555 MBq) and BMIPP (148 MBq). The patients were classified into 3 groups according to PTCA therapy and the interval between the onset of infarction and RI injection (OR time). Group A (n = 56) included patients whose OR time was less than one month and who had undergone successful PTCA, Group B (n = 36) had OR times of less than one month and had conservative medical therapy, and Group C (n = 38) had OR times of over one month. The severity scores of the dual-isotope images were calculated from the defect scores in 9 segments. From the ECG-gated SPECT data with sestamibi, the left ventricular ejection fraction (LVEF; %) and regional wall motion were determined automatically using the QGS program LVEF obtained from gated SPECT correlated well with the severity scores for sestamibi and BMIPP (r = -0.68 and -0.76, respectively). The delta severity scores (BMIPP scores - sestamibi scores) of Group A were significantly higher than those of the other two groups (3.6 +/- 3.0 vs. 1.5 +/- 1.7 and 1.0 +/- 1.4, p < 0.001 ). The rate of dysfunctional segments with normal sestamihi distribution was significantly higher in Group A than in Group C (20.7% vs. 6.7%, p < 0.001). ECG-gated dual-isotope SPECT is useful since myocardial perfusion, fatty acid metabolism and left ventricular function can be analyzed during a single examination, so that this procedure has the potential to provide comprehensive information when evaluating patients with ischemic heart disease.     

Technetium-99m mercaptoalbumin as a potential substitute for technetium-99m labelled red blood cells

Technetium-99m labelled red blood cells (^99mTc-RBCs) are far superior to ^99mTc-labelled human serum albumin (^99mTc-HSA) for radionuclide ventriculography, but their labelling is more complex, time consuming and risk bearing (in vitro labelling) or suffers from interference by some medications (in vivo labelling). We have now modified HSA by the introduction of mercapto groups with the purpose of preparing stable and practical ^99mTc-mercaptoalbumin with long retention in the vascular system, that could replace ^99mTc-RBCs. HSA was incubated with N-succinimidyl S-acetylthioacetate (SATA) or N-succinimidyl 2,3-di(S-acetylthio) propionate (SATP) to introduce a chain containing one or two protected sulfhydryl groups on some of the lysine amino groups. After purification by size-exclusion chromatography (SEC), the mercapto groups were deprotected by incubation at alkaline pH or by treatment with hydroxylamine. The reaction products were used with or without SEC purification for direct or exchange labelling experiments with ^99mTc at neutral pH. SEC-HPLC was used to determine labelling yields and to isolate pure ^99mTc-mercaptoalbumin. Stable ^99mTc-mercaptoalbumin complexes could be formed in 90%–95% yield after coupling albumin with SATA or SATP in all molar ratios used followed by deacetylation in one of the mentioned conditions. The most favourable results were obtained after reaction of SATA or SATP with HSA in a 25: 1 ratio and deprotection with NH₂OH. The stability of the resulting ^99mTc-mercaptoacetyl-albumin (^99mTc-MAHSA) and ^99mTc-dimercaptopropionyl-albumin (^99mTcDMP-HSA) and their retention in vivo in plasma of mice and rabbits are clearly higher than that of conventional ^99mTc-HSA preparations. ^99mTc-DMP-HSA approaches the behaviour of ¹²⁵I-HSA quite well in both animal species. A preliminary study with ^99mTc-DMP-HSA in a volunteer showed a retention in the vascular compartment almost identical to that of ^99mTc-RBCs and clearly higher than that of a common ^99mTc-HSA preparation. The results indicate that these ^99mTc-mercaptoalbumins and especially ^99mTc-DMP-HSA are very promising as a practical alternative to ^99mTc-RBCs.K.A. Verbeke is a Research Assistant for the Belgian National Fund for Scientific Research     

Direct comparison of technetium 99m-sestamibi and technetium 99m-tetrofosmin cardiac single photon emission computed tomography in patients with coronary artery disease

Background  Technetium 99m-labeled sestamibi and tetrofosmin tomography have shown high diagnostic accuracy in the detection of coronary artery disease (CAD). However, few data are available comparing sestamibi and tetrofosmin imaging in the same patients. The aim of the study was to determine the image quality of the two tracers and to compare the results of exercise sestamibi and tetrofosmin tomography in the same patients. Methods  The results of exercise-rest sestamibi and tetrofosmin myocardial tomography were compared in 32 patients with suspected or known CAD who underwent coronary angiography. Image quality was evaluated subjectively. Regional tracer distribution was visually assessed and quantitatively measured in 22 segments/patient. Results  At coronary angiography 7 patients had normal coronary vessels, 11 single-vessel, and 14 multivessel CAD (≥50% luminal stenosis). Image quality judged visually was comparable with the two tracers. Heart/lung and heart/liver ratios for sestamibi and tetrofosmin were not different. At visual analysis, 68% of the patients with CAD had abnormal findings with sestamibi and 76% with tetrofosmin (p=NS). At quantitative analysis, 92% of the patients with CAD had abnormal findings with sestamibi and 96% with tetrofosmin (p=NS). At both visual and quantitative analyses, sensitivity, specificity, and diagnostic accuracy in the detection of individual stenosed vessels were not different between the two tracers. Moreover, for both tracers sensitivity, specificity, and diagnostic accuracy in the detection of diseased vessels were significantly higher (all p<0.05) at quantitative compared with visual analysis. Finally, defect size and severity were similar for the two tracers. Conclusions  Exercise-rest sestamibi and tetrofosmin tomography yielded images of comparable quality and provided similar results in the identification of patients with CAD and in the detection of the individual stenosed coronary vessels.     

Role of 99mTc-sestamibi SPECT in accurate selection of primary hyperparathyroid patients for minimally invasive radio-guided surgery

Purpose A prerequisite for optimum minimally invasive radio-guided surgery (MIRS) for primary hyperparathyroidism (PHPT) is the demonstration of significant uptake of ^99mTc-sestamibi in a parathyroid adenoma (PA). The aim of this study was to evaluate the clinical role or ^99mTc-sestamibi SPECT in selecting patients for this procedure. Methods Fifty-four consecutive PHPT patients were evaluated by single-session ^99mTc-pertechnetate/^99mTc-sestamibi planar subtraction scintigraphy, followed by ^99mTc-sestamibi SPECT acquisition to localise hyperfunctioning PAs and assist in planning the surgical approach. Results Scintigraphy showed the presence of a solitary PA in 47/54 patients (87%) and two or more PAs in four patients (7.4%); it was negative in the remaining three patients (5.6%). The overall sensitivity of ^99mTc-sestamibi scintigraphy was 94.6%. In 7/54 patients, the PA was located deep in the para-oesophageal/paratracheal space. So far, 22 patients with scintigraphic evidence of a solitary PA (in four of whom the PA was located deep in the neck) have undergone successful MIRS using the low 37 MBq (1 mCi) ^99mTc-sestamibi dose protocol. Intraoperative quick parathyroid hormone (QPTH) assay demonstrated a fall in all 22 patients, thus confirming successful removal of the hyperfunctioning PA. No major surgical complications were observed. After a period of follow-up ranging between 6 and 27 months (median 13 months), no case of persistent/recurrent PHPT was recorded. When comparing the parathyroid to background (P/B) ratio measured at planar and SPECT preoperative scintigraphy with that measured intraoperatively with the gamma probe, a good linear correlation was found between the SPECT and the intraoperative gamma probe measurements (r=0.89; p<0.01) but no correlation was found with planar scintigraphic data. Conclusion Our preliminary data suggest that measurement of the P/B ratio by means of ^99mTc-sestamibi SPECT is more accurate in predicting the intraoperative measurements with the gamma probe. In this respect, a preoperative ^99mTc-sestamibi SPECT acquisition should be recommended for better selection of PHPT patients in whom a MIRS approach can be offered.     

Evaluation of regional myocardial perfusion in patients with severe left ventricular dysfunction: Comparison of 13N-ammonia PET and 99mTc sestamibi SPECT

Objective

Positron emission tomography (PET) scanning with ¹³N-ammonia and ¹⁸FDG is well established for the detection of myocardial viability. Due to the limited availability of PET facilities, recent studies have combined technetium 99m sestamibi single photon emission computed tomography (SPECT) with ¹⁸FDG PET or ¹⁸FDG SPECT. This approach enables simultaneous assessment of regional myocardial blood flow and metabolism and substantially increases the capacity for viability detection. To validate whether ^99mTc-Sestamibi SPECT can replace ¹³N-ammonia PET, we compared these two modalities in patients with severe left ventricular dysfunction due to coronary artery disease.

Materials and Methods

Thirty-one patients (mean age 57±8 years; mean ejection fraction 27%±8%) with angiographically verified coronary artery disease were included. In random order, ammonia-PET and sestamibi-SPECT scans were performed. In a 20-segment model of the left ventricle, two blinded observers scored a total of 610 segments on a five-point scale. In a subset of 20 patients, 400 segments were scored twice to evaluate the observer variations of the two techniques. Segmental score differences were used to compare the imaging modalities. The impact on viability detection was assessed by combining the two flow tracers with FDG PET.

Results

Segmental comparison of the PET and SPECT studies yielded similar (difference ≤1) results in 74% of segments, reflecting regional concordance values in the lateral, apical, anterior, septal, and inferior myocardial walls of 86%, 82%, 71%, 66%, and 63%, respectively. The differences in the septal and inferior walls were primarily due to overestimation of perfusion defects by sestamibi SPECT, which yielded a higher proportion of mismatch patterns in those regions. The overall observer variations of the PET and SPECT studies were 7.5% and 5.8%.

Conclusion

Myocardial perfusion imaging with ¹³N-ammonia PET and ^99mTc-sestamibi SPECT yielded similar results in patients with severe left ventricular dysfunction, except for the septal and inferior regions. In these regions, SPECT tended to overestimate perfusion defects. Hence, attenuation correction should be considered when combining FDG PET and sestamibi SPECT for diagnosing myocardial viability to avoid overestimation of mismatch patterns in those regions.     

Two phase imaging of<Superscript>99m</Superscript>Tc-SESTAMIBI and<Superscript>123</Superscript>I-BMIPP for patients with angina pectoris

We saw three cases of angina pectoris in which 99mTc-SESTAMIBI delayed images at rest were useful in diagnosing ischemia risk areas. These findings indicated that delayed 99mTc-SESTAMIBI images may be more sensitive to slight ischemia than 123I-BMIPP images, and suggested that imaging with 99mTc-SESTAMIBI twice at rest may be more effective. The addition of 123I-BMIPP SPECT was considered to be useful in making an evaluation of the severity of ischemia.     

Myocardial 99mTc-sestamibi extraction and washout in hypertensive heart failure using an isolated rat heart

PurposeMyocardial mitochondria are the primary part of energy production for healthy cardiac contraction. And mitochondrial dysfunction would play an important role in progressive heart failure. In the recent years, myocardial washout of ^99mTc-sestamibi [(^99mTc-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI)] has been introduced to be a potential marker in patients with heart failure. The objective of this study was to clarify MIBI extraction and washout kinetics using isolated perfusion system in hypertension induced model of myocardial dysfunction.MethodsSix-week-old Dahl-salt sensitive rats, allotted to 4 groups; a 5-week high-salt group (5wk-HS), 12-week high-salt group (12wk-HS) and two age-matched, low-salt diet control groups (5wk-LS and 12wk-LS). The rats in 5wk-HS and 12wk-HS groups were fed a high-salt diet (containing 8% NaCl). Cardiac function was examined by echocardiography before removing heart. Hearts were perfused according to the Langendorff method at a constant flow rate, in which 20-min MIBI washin was conducted followed by 25-min MIBI washout. Whole heart radioactivity was collected every sec by an external gamma detector. The myocardial extraction, K₁ (ml/min) and washout rate, k₂ (min^?1) were generated.ResultsHigh-salt diet groups showed significant high-blood pressure. Echocardiography revealed thickened LV walls in 5wk-HS, and reduced cardiac function in 12wk-HS, compared to each age-matched control group. K₁ showed no significant difference among all groups (5wk-HS: 2.36±1.07, 5wk-control: 2.59±0.28, 12wk-HS: 1.91±0.90, and 12wk-control: 2.84±0.57). k₂ in 5wk-HS was comparable to that in the age matched control group (0.00030±0.00039 vs ?0.000010±0.00044), but it was increased remarkably in 18wk-HS compared to the age matched control group (0.0025±0.0011 vs 0.000025±0.000041, P<.01), and 5wk-HS (P<.01).ConclusionIn the course of hypertensive heart disease, MIBI washout was increased in the transitional state from hypertrophied to dilated and failing heart, while MIBI extraction remained intact.     

Predictive value of 99mTc-sestamibi scintigraphy for healing of extremity amputation

Purpose Although various non-invasive procedures have been proposed to determine the optimal level of amputation of limbs in patients who have vascular disease, currently there are no consistent criteria that can be applied before surgery. The purpose of this study was to determine whether ^99mTc-sestamibi imaging can accurately predict the healing of amputation sites. Methods In a prospective study in 26 patients (21 men, 5 women; age range 23–94 years) presenting with ulcers or gangrene of the foot and hand, ^99mTc-sestamibi imaging was performed preoperatively. The indications for amputation included gangrene (23 patients), electrical injury (2 patients) and trauma (1 patient) of extremities. Although the amputation levels were chosen according to clinical criteria and scintigraphic results, the final amputation level was defined by scintigraphic results. Two below-knee, one above-knee, 12 toe, 11 transmetatarsal, two phalanx, one finger and one thumb amputations and one shoulder disarticulation were performed. In four cases, the amputation defect was not suitable for coverage using a local dermal flap; rather, it was covered with free tissue transfer. Patients had clinical follow-up for 6–36 months (mean 11.69 months) to assess healing of the stump. Scan results were compared with clinical outcome to assess prediction of healing. Results There was healing in all amputations at the end of the follow-up period. When evaluated regarding preoperative ^99mTc-sestamibi uptake pattern, there was no perfusion to the lesion site in 21 patients and perfusion to an area smaller than the extent of skin necrosis in four patients; thus, in these 25 patients, ^99mTc-sestamibi scintigraphy suggested non-viable tissue in the extremities with clear-cut edges of perfused muscle tissue. Diffusely decreased uptake was seen below the left knee in one case. How scintigraphy changed management was analysed. The amputation levels proposed before scintigraphy were divided into two groups, “definite” (n=14) and “indefinite” (n=12), based on visual examination and Doppler findings. In nine patients in the definite group, the proposed amputation level before scintigraphy was not altered by the scintigraphic data. However, ^99mTc-sestamibi scan enabled unnecessarily high amputation levels to be avoided in 12 patients in the indefinite group and in five patients in the definite group. Therefore, there was change in management of 65% of cases based on scintigraphic findings. Conclusion Since healing of the stump was seen in all cases, outcome was correctly predicted by scintigraphy. This preliminary study supports the use of ^99mTc-sestamibi scan in selecting the optimal amputation level consistent with subsequent stump healing.     

Reduction of <Superscript>99m</Superscript>Tc-sestamibi and <Superscript>99m</Superscript>Tc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of ^99mTc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, ^99mTc-tetrofosmin (TF), was also examined. Cellular uptake of ^99mTc-MIBI and ^99mTc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N₂ and 5% CO₂ reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.     

Myocardial uptake characteristics of three99mTc-labeled tracers for myocardial perfusion imaging one hour after rest injection

OBJECTIVE: 99mTc-tetrofosmin and 99mTc-sestamibi are approved tracers for myocardial perfusion studies. Recently, a 99mTc-MIBI preparation from a different manufacturer (99mTc-cardiospect-MIBI) has been introduced to the market. Therefore, the aim of this study was the evaluation of 99mTc-tetrofosmin as well as of two different 99mTc-labeled MIBI tracers with regard to differences in imaging quality under resting conditions. METHODS: Sixty patients (mean age 63.8 years +/- 1.25) with known or suspected coronary artery disease but without evidence of rest-ischemia were included. Twenty patients in each group were examined by a two-day-rest-stress protocol using the three 99mTc-labeled tracers. Visual analysis of all images was performed by two experienced physicians blinded with regard to the applied tracer. Regions of interest (ROI) were defined over the heart, lung and whole body only in the rest imaging in order to calculate heart-to-lung, lung-to-whole body-, and heart-to-whole body-ratios. RESULTS: The heart-to-lung ratio was statistically significant higher for 99mTc-cardiospect-MIBI as compared to 99mTc-sestamibi as well as to 99mTc-tetrofosmin. Furthermore, a significantly higher heart-to-lung ratio was found for 99mTc-sestamibi as compared to 99mTc-tetrofosmin. The heart-to-whole body-ratio and the lung-to-whole body-ratio were equivalent between all tracers. Visual analysis revealed only slight differences regarding image quality between all tracers. CONCLUSIONS: ROI analysis surprisingly revealed a significant higher myocardial uptake and consequently a higher heart-to-lung ratio for 99mTc-cardiospect-MIBI. Whether this leads to a better visual image quality has to be evaluated in future studies with larger study populations as well as semiquantitative segmental analysis of the myocardial perfusion images.     

Unexpected abnormal extra-cardiac mediastinal accumulation of technetium-99m-tetrofosmin in patient with acute pericarditis

A 58-year old woman had felt some chest pains on effort for several days. She was admitted to the emergency room with severe and refractory chest pain after exercise. Electrocardiogram showed marked ST-segment elevations in II, III, aVF and V1-6 electrodes. Echocardiogram revealed neither wall motion asynergy in the left ventricle nor abnormal pericardial effusion. Chest X-ray showed normal findings, and mild elevation of C-reactive protein was observed in the blood chemistry data. Her chest pain was relieved by nitroglycerin administration. Emergent technetium-99m-tetrofosmin myocardial imaging did not show any abnormal perfusion in the left ventricle. However, an abnormal extra-cardiac mediastinal accumulation was detected in the planar image. Contrast-enhanced chest CT scanning also demonstrated an inhomogeneously enhanced tumor in the anterior superior mediastinum. The tumor was surgically removed and was finally diagnosed as an invasive thymoma. Technetium-99m-tetrofosmin scintigraphy happened to provide useful information for diagnosing acute pericarditis with mediastinal tumor.     

99mTc-DTPA and 99mTc-DMSA renal gamma imaging in the surveillance of patients with conduit urinary diversion

We studied renal anatomy and function using ^99mTc-2-3 dimercaptosuccinic acid (DMSA) and ^99mTc-diethylenetriaminepentaacetic acid (DTPA) in 27 patients with conduit urinary diversion. In this condition, free ureteral reflux is often associated with bacteriuria, and these factors are thought to precipitate progressive renal deterioration. Gamma-camera images provided valuable information concerning the structure of the renal parenchyma, the function of individual kidneys and possible ureteral obstruction, thus helping us to decide whether or not to instigate further treatment. The information gained using renal gamma imaging with ^99mTc-DTPA and ^99mTc-DMSA was complementary and partly overlapping. We preferred the use of ^99mTc-DTPA because of its ability to visualise the ureters and the region of ureteroconduit anastomosis. Using diuretic medication, we were able to differentiate true ureteral obstruction from atony in 9 patients using ^99mTc-DTPA.     

Comparison between the end-diastolic images and the summed images of gated 99mTc-sestamibi SPECT perfusion study in detection of coronary artery disease in women

BACKGROUND: End-diastolic images (EDI) can be easily derived from technetium 99m-sestamibi gated single photon emission computed tomography (SPECT) perfusion study (SGS). This may reduce the effect of myocardial wall thickening during systole and potentially improve the sensitivity of radionuclide perfusion imaging, especially in patients with small hearts. METHODS: This prospective study was conducted in 53 consecutive female patients to compare the diagnostic accuracy of EDI with that of the summed images (SI) of SGS. Fifty-three patients with suspected coronary artery disease (CAD), scheduled for coronary angiography within 2 months, were evaluated with SGS. Treadmill stress testing was used in 28 patients, and dipyridamole injection was used in the remaining 25 patients. A 2-day protocol was used as follows: stress test with 25 to 30 mCi of 99mTc-sestamibi and a rest study performed at least 24 hours later with the same dose. Sixteen frames per cardiac cycle were acquired for both the rest and the stress studies. Three end-diastolic frames were used for EDI, and all the 16 frames were summed for SI. SI and EDI data reconstruction were interpreted by 3 experienced blinded observers (consensus reading) during two distinct reading sessions, one with SI alone and the second with EDI alone. The heart was divided into 17 segments. RESULTS: Coronary angiography showed > or = 50% stenoses in 1 or more major coronary arteries in 38 patients and was normal in 15 patients. The sensitivity was 73.7% (28/38) and 84.2% (32/38), respectively, for SI and EDI. Three of 4 patients with CAD not detected by SI but seen with EDI were considered to have relatively small hearts. The specificity was 86.7% (13/15) and 80.0% (12/15) for SI and EDI, respectively. On a total of 901 segments, 106 ischemic defects were detected by SI and 173 by EDI (P = .001). The segmental agreement between the two techniques was 88.6% (798/901 segments). CONCLUSION: EDI showed more ischemic defects than SI, and there was also a nonsignificant trend toward an improved sensitivity of EDI in comparison to SI in detection of coronary artery disease in women, especially in patients with small hearts. EDI may be a useful adjunct to the standard perfusion imaging with SGS in such a clinical situation.     

99mTc-Diethyl-iodo-HIDA (JODIDA): A new hepatobiliary agent in clinical comparison with 99mTc-diisopropyl-HIDA (DISIDA) in jaundiced patients

The new HIDA derivative, ^99mTc-dimethyl-iodine-HIDA (JODIDA), was compared with ^99mTc-diisopropyl-HIDA (DISIDA) in 17 patients with jaundice by means of paired cholescintigraphic imaging studies. The following parameters were visually assessed: the extent of urinary tract visualization, biliary contrast and appearance time, and gallbladder visualization and appearance time. In the 6 patients with a total bilirubin level of between 19 and 66 mol/l (1.1 and 3.9 mg/dl), both radiopharmaceuticals gave similar results except for the moderate visualization of the urinary tract with DISIDA in contrast to JODIDA. In the remaining 11 patients with a total bilirubin level between 102 and 1303 mol/l (6 and 76 mg/dl), JODIDA showed significant advantages over DISIDA: non-visualization of the urinary tract, stronger and faster biliary contrast, and better gallbladder visualization. JODIDA thus offered substantial diagnostic advantages over DISIDA in 8 of these patients. In 4 patients, the differential diagnosis of jaundice (intrahepatic or mechanical disorder) was possible with JODIDA, whereas DISIDA either could not visualize intestinal or gallbladder activity at all or could not differentiate it from the urinary tract. In one patients, JODIDA offered faster (18 h) diagnosis. In the remaining 3 patients, other, substantially false interpretations could be avoided through the use of JODIDA. Further clinical experience with JODIDA in more than 40 patients confirmed the results of this study. We concluded that JODIDA is of significant advantage over DISIDA in clinical situations such as total bilirubin level above 80–100 mol/l (4.7 to 5.8 mg/dl), examination of small children and critically ill patients and suggestion of bile leakage. As there are also no clinical disadvantages, it could become the rediopharmaceutical of choice for hepatobiliary imaging.     

99mTc-labelling of leucocytes with 99mTc-DPO: a complex developed for myocardial imaging

The lipophilic ^99mTc-DPO complex, developed as a myocardial imaging radiopharmaceutical, was used to label leucocytes. After an incubation of 0.1 ml ^99mTc-DPO (8 g DMPE*2HCl) with mixed leucocytes in plasma, the labelling efficiency was over 70%. During incubation in 5 ml plasma, a loss of activity was found between 20% (1 h) and 35% (3 h) caused by elution. Disturbances of cell viability could not be found with the help of the chemiluminescence test. The in vivo recovery was determined in three dogs and was 45%–50% (0.5 h), 30%–36% (1 h), and 18%–24% (3 h). Autologous ^99mTc-DPO-leucocytes were used on seven patients with suspected osteomyelitis, there were four true negative and three true positive results. The target/nontarget ratio determined by ROI in the positive cases was 1.8 to 2.5 at 3 h after injection.     

Clinical evaluation of technetium-99m infecton for the localisation of bacterial infection

The aim of the study was to distinguish infection from inflammation in patients with suspected infection using technetium-99m Infecton. Ninety-nine patients (102 studies) referred for infection evaluation underwent imaging with 400 MBq^99mTc-Infecton at 1 and 4 h. Most patients had appropriate microbiological tests and about half (56) had radiolabelled white cell scans as well. No adverse effects were noted in any patient. The clinical efficacy of^99mTc-Infecton depended in part on whether imaging was undertaken during intibiotic therapy for infection or not. In consultation with the microbiologist, 5–14 days of appropriate and successful antibiotic therapy was considered adequate to classify some results as true-negatives. The figures for sensitivity and specificity of^99mTc-Infecton for active or unsuccessfully treated infection were 83% and 91% respectively. It is concluded that^99mTc-Infecton imaging contributed to the differential diagnosis of inflammation. It is being used as the first imaging modality when bacterial infection is suspected.     

Imaging of regional lymph node metastases with 99mTc-depreotide in patients with lung cancer

Purpose The aim of this study was to evaluate the clinical usefulness of scintigraphy with ^99mTc-depreotide in the assessment of loco-regional nodal spread in patients with suspected lung cancer in comparison with computed tomography (CT).Methods Eighty-six patients were investigated with single-photon emission computed tomography (SPECT) of the thorax after i.v. injection of 740 MBq ^99mTc-depreotide. The results were evaluated in conjunction with a thoracic CT scan in all 86 patients with 204 lymph node stations. The scintigraphic results were correlated with cytological (38), histological (20) or clinical–radiological (146) findings and compared with CT. The quantitative evaluation of depreotide uptake was performed on 48 cytologically or histologically verified nodal stations from 28 patients by SPECT using region of interest analysis with four different reference regions.Results ^99mTc-depreotide scintigraphy for all 204 investigated lymph node stations had a sensitivity of 99% and a negative predictive value of 98% in determining lymph node involvement. Scintigraphy and CT showed the same level of accuracy, 76.4%. CT findings had a higher positive predictive value but a lower negative predictive value compared to ^99mTc-depreotide scintigraphy. The quantitative evaluation of depreotide uptake in lymph nodes using vertebra as a reference region showed that a cut-off level of 0.56 excludes malignant involvement of lymph nodes, while a cut-off level of 1.66 excludes benign disease in lymph nodes. About 73% of all investigated lymph node stations showed uptake values between these cut-off levels.Conclusion Absence of ^99mTc-depreotide uptake on scintigraphic imaging can exclude regional lymph node involvement with a high degree of probability and may be useful in clinical practice. The quantitative evaluation of depreotide uptake in regional lymph nodes did not increase the diagnostic accuracy of the method in general but did elucidate the lymph node status in some patients.     

Acute oral trimetazidine administration increases resting technetium 99m sestamibi uptake in hibernating myocardium

Background  Trimetazidine is an antiischemic drug protecting the myocardium from ischemic damage through the preservation of mitochondrial oxidative metabolism, without any hemodynamic effect. ^99mTc-sestamibi is accumulated by myocytes according to mitochondrial function. As mitochondrial metabolism is thought to be present in hibernating myocardium, the aim of the study was to investigate trimetazidine effects on infarcted and eventually hibernating myocardial areas by means of ^99mTc-sestamibi perfusional scintigraphy, comparing them to postoperative recovery of wall motion. Methods and Results  Twelve patients with previous myocardial infarction underwent 2 perfusion imaging tomographic studies at rest with ^99mTc-sestamibi, receiving placebo or trimetazidine (60 mg orally), and subsequently underwent revascularization procedures. An echocardiographic study was carried out before and >3 months after revascularization. At polar map analysis of placebo scan, infarcted vascular territories (wall motion score index: 2.65±0.31) showed 73.7%±10.4% of the territory with activity <2.5 SD from the mean of normals, for a severity (expressed as the sum of the standard deviations below average normal values in all abnormal pixels) of 833.8±345.7. Polar map analysis of the trimetazidine scan showed tracer uptake increased significantly in 11 of them, by 8.2%±3.0% (p<0.001) and by 180.3±111.0 SD (p<0.001), respectively. Postoperative wall motion score index improved significantly in 9 of these territories (−0.9±0.4, p<0.001). Conclusions  Trimetazidine-associated increase in ^99mTc-sestamibi uptake in infarcted but viable myocardial areas is probably related to an improvement in mitochondrial oxidative metabolism that is essential to ^99mTc-sestamibi retention. Additionally, coupling trimetazidine administration to ^99mTc-sestamibi perfusional scintigraphy may represent a means of detecting viable myocardium.