Rapid preparation and quality control method for technetium-99m-2-methoxy isobutyl isonitrile (technetium-99m-sestamibi).

Technetium-99m-2-methoxy isobutyl isonitrile (99mTc-sestamibi) is a radiopharmaceutical that can be useful in the evaluation of patients with acute myocardial infarction. The current method for preparation requires a lengthy boiling water bath procedure and the recommended quality control procedure is cumbersome and time-consuming. Using a microwave oven, the heating time necessary to provide a labeling efficiency (averaging 97% for sestamibi-labeled with maximum allowable 99mTc activity and volume has been reduced to 10 sec. A new mini-paper chromatography (MPC) system has been developed to analyze the radiochemical purity of 99mTc-sestamibi involving a 1:1 chloroform/tetrahydrofuran developing solvent. The recommended thin-layer chromatography (TLC) system involving the use of an AI2O3-coated plate requires an average time for drying and development of 34.8 +/- 1.6 min (n = 58) to complete, whereas the new MPC system has an average developing time of 2.3 +/- 0.1 min (n = 26). For radiochemical purity values ranging from 71-99% (n = 31), the MPC and TLC methods correlated closely (r = 0.99) with a regression line of MPC% = 1.05 TLC%--5.75. The combined use of the microwave oven heating method and our quick quality control system will facilitate the rapid, emergency use of 99mTc-sestamibi and eliminate the need for advance preparation of multiple kits each day.     

Identification of viable myocardium in patients with chronic coronary artery disease: comparison of thallium-201 scintigraphy with reinjection and technetium-99m-methoxyisobutyl isonitrile.

We compared the results of 201Tl reinjection and those of 99mTc-methoxyisobutyl isonitrile (MIBI) in identifying viable myocardium in 20 male patients with angiographically proven coronary artery disease (CAD) and left ventricular dysfunction (ejection fraction 30% +/- 8%). All patients had irreversible defects on standard exercise-redistribution thallium imaging. Thallium was reinjected immediately after the redistribution study, and images were reacquired. The patients also underwent stress and rest 99mTc-MIBI myocardial scintigraphy (2-day protocol). A total of 300 myocardial regions were analyzed, of which 122 (41%) had irreversible thallium defects on redistribution images before reinjection. Of the 122 myocardial regions with irreversible defects on standard stress-redistribution thallium cardiac imaging, 65 (53%) did not change at reinjection and 57 (47%) demonstrated enhanced uptake of thallium after reinjection. Of the same 122 irreversible defects on stress-redistribution thallium, 100 (82%) appeared as fixed defects and 22 (18%) were reversible on 99mTc-MIBI myocardial scintigraphy. These data indicate that 201Tl cardiac imaging with rest reinjection is superior to 99mTc-MIBI myocardial scintigraphy in identifying viable myocardium in patients with chronic CAD, suggesting that regions with severe reduction of 99mTc-MIBI uptake both on stress and rest images may contain viable myocardium.     

Myocardial perfusion imaging with a new radiotracer, technetium-99m-hexamibi (methoxy isobutyl isonitrile): comparison with thallium-201 imaging

Technetium-99m-hexamibi (methoxy isobutyl isonitrile) is a Tc-99m-hexakis analog that can be used as a myocardial perfusion imaging agent. This is a report of an initial study that was performed in four institutions to assess the feasibility of Tc-99m-hexamibi myocardial imaging for the detection of coronary artery disease in patients undergoing treadmill stress test. Thirty-three patients referred for evaluation of chest pain had two exercise stress tests, one with Tl-201 and at least 24 hours after, and a second one with Tc-99m-hexamibi. Myocardial planar imaging started 60 minutes after injection at stress of 10-20 mCi of Tc-99m-hexamibi. Because this agent does not redistribute in myocardium after a stress injection, a second injection of 10-20 mCi of Tc-99m-hexamibi was performed with the patient at rest a few days later. Qualitative assessment of both Tl-201 and Tc-99m-hexamibi myocardial distribution was performed in 297 left ventricle segments (three segments of each of three views). There was a good correlation for the presence of normality, scar, or ischemia with the two radiopharmaceuticals, both on a segment by segment (259/297, or 87.2%) and patient-by-patient basis (29/33, or 87.9%). The number of segments found ischemic with Tl-201 and with Tc-99m-hexamibi were nearly equal, as were the number that were normal with one radiopharmaceutical and ischemic by the other. This initial study demonstrates that it is possible to detect stress-induced abnormalities of myocardial perfusion with Tc-99m-hexamibi similar to Tl-201 imaging.     

Demonstration of reperfusion after thrombolysis with technetium-99m isonitrile myocardial imaging

Technetium-99m isonitrile myocardial perfusion imaging was employed in a patient undergoing thrombolytic therapy with recombinant tissue plasminogen activator for acute anteroseptal myocardial infarction. Technetium-99m isonitrile does not demonstrate significant myocardial redistribution after intravenous injection. The imaging agent was administered in the emergency room, prior to the initiation of thrombolytic therapy. The initial area at risk for infarction was visualized on images obtained after the patient had been effectively treated. Imaging performed 5 days later, after repeat injection of [99mTc]isonitrile, showed a smaller myocardial perfusion defect indicating salvage of myocardium. Thus, this technique offers promise as a noninvasive means of assessing the area at risk, the success of reperfusion, and the presence of salvaged myocardium, early in the course of acute myocardial infarction.     

Myocardial infarct imaging with technetium-99m phosphates

Technetium-99m-phosphate imaging is particularly valuable in detecting (1) small transmural infarcts (3 g and larger in size); (2) new acute transmural infarcts in or near regions of old infarction; (3) acute subendocardial infarcts (larger than 3 g in size); (4) acute infarction in patients with left bundle branch block; and (5) perioperative myocardial infarction. Localization of inferior and posterior myocardial infarction is improved with imaging. Sizing of acute anterior and lateral infarcts has been accurately done in dogs and should prove helpful in patients. Extensive evaluation in both experimental animals and in patients has shown 99mTc-phosphate myocardial imaging to be a useful clinical tool, and it may be one of the most sensitive noninvasive ways presently available to identify acute myocardial necrosis. It is important to understand that 99mTc-phosphate imaging has a different pathophysiology basis from EKG's or serum enzymes. These tests do not compete but instead should complement one another.     

A new technetium-99m labeled isonitrile complex 99mTc-TMCHI as a potential blood pool imaging agent.

A new isonitrile ligand 3,3,5-trimethyl cyclohexylisonitrile (TMCHI) and its copper salt [Cu(TMCHI)4BF4] were synthesized and characterized by IR and elemental analysis. 99mTc-TMCHI is prepared by direct labeling method with high RCP. In vitro protein binding in albumin, blood retention and biodistribution of 99mTc-TMCHI in mice indicated that it is mainly accumulated and maintained in blood with a high protein binding rate and low washout rate. The target/non-target ratios in mice are excellent and suggest its use as a cardiac blood pool agent.     

Simultaneous assessment of wall motion and myocardial perfusion by technetium-99m methoxy isobutyl isonitrile

The aim of this study was to assess whether or not myocardial uptake of Technetium-99m methoxy isobutyl isonitrile (Tc-MIBI) indicated myocardial viability. We performed simultaneous Tc-MIBI angiography and myocardial SPECT at rest on 12 patients with suspected coronary artery disease. Left ventricle was divided into 3 segments, and regional wall motion was graded as normal, hypokinesis and akinesis/dyskinesis. Myocardial uptake of Tc-MIBI was assessed as normal, reduced and absent in each segment. In segments with normal and reduced Tc-MIBI uptake, 7% (2 of 28) and 33% (2 of 6) showed wall motion abnormalities of akinesis/dyskinesis, respectively. However, all segments with absent Tc-MIBI uptake had asynergy of akinesis/dyskinesis (2 of 2, 100%). Myocardial Tc-MIBI uptake at rest indicated wall motion abnormalities and was considered to be useful for the evaluation of myocardial viability. First-pass radionuclide angiography followed by myocardial SPECT with Tc-MIBI demonstrated to be useful for the simultaneous assessment of the left ventricular wall motion and myocardial perfusion.     

Prescintigraphic morphine application for abdominal adenocarcinoma imaging, with technetium-99m methoxy isobutyl isonitrile

Imaging of tumors with cationic tracers, especially with technetium-99 methoxy isobutyl isonitrile ((99m)Tc-MIBI), revealed high specificity for the diagnosis and follow up of various malignancies. However, these radiopharmaceuticals are of limited value for the diagnosis of malignancies of the abdominal region due to the immediate biliary secretion of the tracer and the associated high background activity. In a prospective, single-blinded protocol, patients with endoscopically diagnosed gastrointestinal malignancies were assigned to undergo (99m)Tc-MIBI imaging of the abdomen. To overcome biliary secretion of cationic tracer we administered 0.04 mg/kg morphine hydrochloride intravenously before the administration of 600 MBq (99m)Tc-MIBI. Planar images were performed in the anterior and posterior views with a double-headed gamma camera and with 3 min acquisition time, followed by single photon emission tomography images (3 degrees, 20 sec/frame). Results were compared to findings of endoscopy, computed tomography scan and surgery. Twenty four patients 17 male and 7 female , mean age 69 years, range 52-83, years were enrolled. All patients suffered from adenocarcinoma, (19 from colorectum, 3 from gastric, 1 from pancreatic and one patient had both gastric and colorectal adenocarcinoma, for a total of 25 tumor lesions). The primary objective- inhibition of biliary secretion- was achieved in 23 of the 24 patients. (99m)Tc-MIBI-imaging was accumulated intra-abdominally in 19 patients. In 2 patients the tumor was endoscopically completely removed before the scan. In these two patients (99m)Tc-MIBI imaging showed no intra-abdominal tracer accumulation. When compared to the endoscopic findings, (99m)Tc-MIBI imaging showed time positive results in 13 of the 23 remaining individual tumor lesions, false positive in 6 and false negative in 4. This study showed a sensitivity of 57% and a specificity of 20% of the above technique for the identification of intra-abnominal adenocarcinomas. Correct diagnosis did not correlate with tumor size. In conclusion, prescintigraphic morphine administration inhibits background activity coming from biliary secretion, and enables better intra-abdominal (99m)Tc-MIBI imaging but with limited sensitivity and poor specificity.     

Myocardial infarct imaging in patients with technetium-99m 2,3-dimercaptosuccinic acid. Superiority of technetium-99m pyrophosphate

Technetium-99m 2,3-dimercaptosuccinic acid (Tc-99m DMSA) has been used successfully for imaging acute myocardial infarction in a canine model. The application in humans, however, has not been previously reported. In order to determine the feasibility of using this agent in clinical studies and to compare the agent to technetium-99m pyrophosphate (Tc-99m PPi), ten patients with proven myocardial infarction were studied. While imaging of transmural infarctions in humans was achieved using Tc-99m DMSA, scores for the Tc-99m DMSA images (1.8 +/- 0.96) were not as high as for Tc-99m PPi (2.5 +/- 0.45) (P less than 0.05). Discordance among four independent interpreters was greater for images obtained with Tc-99m DMSA. The superiority of Tc-99m PPi was evident whether images were obtained early (within 24 hours) or late (within five days). Although DMSA images were not obscured by rib uptake, they were less sensitive (63%) than Tc-99m PPi (97%). A potential advantage of Tc-99m DMSA in imaging acute myocardial infarction is that radiotracer concentration in the infarct occurs primarily in the early postinfarction period. The longer postinfarction that Tc-99m DMSA imaging was attempted, the lower the concentration of radiotracer. Thus, Tc-99m DMSA would not be expected to have the same persistence pattern as Tc-99m PPi into the remote postinfarction period. The persistent positivity of Tc-99m PPi has made it difficult to diagnose reinfarction.     

Quantitative planar imaging with technetium-99m methoxyisobutyl isonitrile: comparison of uptake patterns with thallium-201

To compare the myocardial uptake pattern of 99mTc-labeled methoxyisobutyl isonitrile [( 99mTc] MIBI) and 201TI, planar scintigraphy were performed in both patients with documented coronary artery disease and subjects with a low likelihood of disease. Quantitative analysis was employed using a standard interpolative background subtraction algorithm and a new algorithm modified to better accommodate for the differences in extracardiac activity seen with [99mTc]MIBI rest images. Among patients with coronary artery disease, the standard algorithm yielded no significant difference in relative defect magnitude between [99mTc]MIBI and 201TI on stress scintigrams (p = 0.48), although the magnitude of [99mTc]MIBI defects was greater on resting images (p = 0.02). When the modified algorithm was employed, defect magnitude was similar for both stress (p = 0.91) and rest (p = 0.20) images. Normal segmental uptake ratios derived from a comparison of contralateral segments (e.g., septal:posterolateral) in the low likelihood patients were similar for both [99mTc]MIBI and 201TI. Thus, modification of the standard interpolative background subtraction algorithm is necessary for quantitative planar [99mTc]MIBI perfusion imaging. When appropriate background subtraction is employed, myocardial uptake and quantitative defect magnitude of [99mTc]MIBI and 201TI planar images are similar.     

Myocardial clearance of Tc-99m hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI) in patients with coronary artery disease

Myocardial clearance of the new cationic, lypophilic myocardial perfusion agent, Tc-99m-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI) was studied in nine patients with coronary artery disease. Regional time-activity curves were determined from serial postexercise myocardial SPECT images after a single dose of Tc-99m MIBI. There were significant differences between the clearance rates from normal and ischemic myocardium. Tc-99m MIBI washout from normal myocardium was 27 +/- 8% by 6 hours after injection. Clearance from mild myocardial defects (initial activity greater than 60% of the activity in normal myocardium) was 16% by 6 hours in six patients. No washout was detected by 6 hours in the three patients with severe myocardial defects. The ratio between the activity in ischemic and normal myocardium increased from 0.70 +/- 0.08 to 0.80 +/- 0.13 and 0.84 +/- 0.13 at 4 and 6 hours after injection in the patients with mild defects. In the patients with large defects, the ratio increased from 0.42 +/- 0.09 to 0.54 +/- 0.07 at 6 hours. It is concluded that, while redistribution is substantially slower than with Tl-201, image interpretation and data evaluation should be approached cautiously when imaging is delayed 4 hours or more after injection of Tc-99m MIBI. Quantitative techniques aimed at evaluating the extent and intensity of myocardial ischemia will be particularly affected.     

The localization of myocardial ischaemia with technetium-99m methoxy isobutyl isonitrile and single photon emission computed tomography

Thirty-two patients with suspected coronary artery disease were studied by single photon emission computed tomography (SPECT) imaging with oblique reconstructions of the myocardium following the intravenous administration of technetium-99m methoxy isobutyl isonitrile at peak exercise. All patients also underwent three-vessel coronary angiography. The SPECT technique produced very detailed images allowing easy delineation of localized myocardial defects. Segmental myocardial uptake defects were compared with diseased vessels as shown at angiography. A good correlation was shown between right coronary artery (RCA) disease and mid and proximal inferior segments and between left circumflex (LCx) artery disease and mid and proximal lateral segments, allowing accurate localization of a defect to one of these two vessels' territories. Sensitivity and specificity of detection of disease of the RCA and LCx artery were high. Defects associated with a lesion of the left anterior descending vessel were more variable.     

Visualization of suppressed thyroid tissue by technetium-99m-tertiary butyl isonitrile: an alternative to post-TSH stimulation scanning

The autonomously functioning thyroid nodule (AFTN) is a discrete, nodular structure which operates independently of pituitary control and without relation to the remaining thyroid tissue. Presently, for the visualization of a suppressed thyroid lobe, a patient has to undergo the thyrotropin (TSH) stimulation test, which has several disadvantages. In this study we have used tertiary butyl isonitrile (99mTc-TBI), well known as a myocardial imaging agent, for visualization of the suppressed lobe. Thirteen of fourteen patients studied demonstrated a contralateral lobe on a 99mTc-TBI scan which was not visualized with a 99mTc0(4) or 131I scan. Although it is not possible to demonstrate the autonomous nature of the hyperfunctioning thyroid nodule using 99mTc-TBI, we conclude that it is feasible to use this agent to visualize the lobe without the TSH test.     

Washout and redistribution between immediate and two-hour myocardial images using technetium-99m sestamibi

The aim of this study was to assess whether a clinically relevant change in myocardial sestamibi activity could be documented within the first 120 min following injection (p.i.). In 17 patients planar anterior imaging of the heart was performed 5 min and 120 min p.i. During this time interval, mean decay-corrected myocardial activity declined to 77.9%±9.7% after stress and to 85.7%±7.9% after injection at rest (P<0.05). In 19 patients with angiographically documented coronary artery disease, single-photon emission tomography was performed 5 min and 120 min after injection at maximum stress. For analysis, sestamibi activity was scored semiquantitatively in six left ventricular segments. Furthermore, sestamibi uptake was assessed quantitatively using a circumferential profile method. In 35 of 114 segments the score improved within 120 min p.i. (early fillin); in these segments relative sestamibi activity rose from 69.9%±22.5% to 74.5%±20.8% (P<0.01). In five patients this early fill-in was the only sign of exercise-induced hypoperfusion. In 7 of 114 segments the score deteriorated 120 min p.i. (early tracer washout); in these segments relative sestamibi activity declined from 85.6%±9.9% to 80.1%±10.7% (P<0.02). In three of four patients with early tracer washout the corresponding coronary artery was significantly narrowed. In conclusion, a global myocardial sestamibi washout was registered within the first 120 min after injection. A fill-in of initial defects as well as an early tracer loss could be detected in a relevant number of patients with chronic coronary artery disease during the first 2 h p.i. In these patients the extent of detected reversible perfusion abnormality depends on the chosen time interval between injection and imaging. The results of this study suggest that exercise imaging should be started immediately after injection.     

Myocardial uptake of technetium-99m stannous pyrophosphate in experimental viral myopericarditis.

Distribution of technetium-99m stannous pyrophosphate was studied in mice with experimentally induced viral myopericarditis. Myocardial and bone uptakes of Tc-PPi were compared in 55 mice inoculated with coxsackievirus B3 (Nancy strain). The myocardium-to-bone uptake ratio in 33 mice with myopericarditis was increased to a greater extent than that seen in 22 mice without myopericarditis (p less than 0.001). In the severely involved heart, the uptake per gram exceeded that in the bone. Myocardial uptake in myopericarditis can be visualized on a whole-body image using a pinhole collimator and a left lateral view. Our experimental studies suggest the potential clinical usefulness of myocardial scintigraphy in viral myopericarditis.     

Clinical comparison of technetium-99m-N,N-bis(mercaptoacetyl)-2,3-diaminopropanoate with technetium-99m DTPA for renal imaging

We studied 14 patients having serum creatinines of 1.0 to 12.8 mg/dl with either Tc-99m-N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate (CO2-DADS) or Tc-99m DTPA, and within 48 hours with the other agent. Analog and digital images of the kidneys and bladder were acquired for 30 minutes after injection and after voiding. The kidney-to-background ratio at 3 minutes for Tc-99m CO2-DADS was 2.01 +/- 0.79 (mean +/- SD) times that for Tc-99m DTPA (P less than 0.001). The parenchymal transit time for Tc-99m CO2-DADS was 1.34 +/- 0.25 (mean +/- SD) times that for Tc-99m DTPA (P less than 0.005). The percent-excreted dose at 30 minutes for Tc-99m CO2-DADS was 2.57 +/- 1.24 (mean +/- SD) times that for Tc-99m DTPA (P less than 0.001). Analog Tc-99m CO2-DADS images showed spatial resolution comparable to that for Tc-99m DTPA. Hepatobiliary excretion was never seen. Tc-99m CO2-DADS appears to be generally superior to Tc-99m DTPA as a renal radiopharmaceutical.     

Splenic uptake of both technetium-99m diphosphonate and technetium-99m sulfur colloid in sickle cell beta (0) thalassemia

A 19-year-old black woman with sickle cell beta(0) thalassemia had experienced more than 100 hospital admissions for sickle cell crisis and aseptic necrosis of both femoral heads. Her spleen was enlarged threefold and accumulated both radiocolloid and bone-seeking agent on two occasions, demonstrating an exception to the rule in sickle cell anemia that spleens that take up bone-seeking agents demonstrate functional asplenia. In the context of fever, left upper quadrant pain, and splenomegaly, the pattern of calcification in the patient's spleen as revealed in ultrasound and CT studies suggested possible abscess and led to unnecessary splenectomy. The nuclear medicine studies did not support this diagnosis. Nuclear medicine physicians should not be misled by splenic findings of sickle cell thalassemia (and possibly of other heterozygous sickle cell disorders) that differ from those of the more familiar homozygous sickle cell anemia.