Technetium-99m red blood cell venography in upper extremity deep venous thrombosis

The efficacy of Tc-99m RBC venography has been demonstrated with respect to the study of lower extremity deep venous thrombosis. A case is presented where Tc-99m RBC venography was used to study the upper as well as lower extremities in a patient with upper extremity deep venous thrombosis (DVT) who was found to have pulmonary embolism.     

Technetium-99m HM-PAO-labeled leukocytes in detection of inflammatory lesions: comparison with gallium-67 citrate

Forty-three patients with suspected benign, inflammatory, or infectious diseases were imaged with [99mTc]HM-PAO-labeled leukocytes and [67Ga]citrate. Technetium-99m leukocytes showed 22 true-positive, no false-positive, 19 true-negative, and two false-negative findings and [67Ga]citrate 23, 7, 12 and 1, respectively. The sensitivity, specificity, and accuracy values with 99mTc leukocytes were 92%, 100%, and 95%, and with [67Ga]citrate 96%, 63%, and 81%. Technetium-99m leukocyte scintigraphy has a promising future in comparison with [67Ga]citrate because of the ready availability of [99mTc]HM-PAO, the good image quality, more rapid results (within few hours), and the lower radiation exposure to the patient with 99mTc leukocytes. The usefulness of 99mTc leukocytes in chronic osteomyelitis needs further evaluation.     

Technetium-99m hexakis 2-methoxyisobutyl isonitrile: human biodistribution, dosimetry, safety, and preliminary comparison to thallium-201 for myocardial perfusion imaging

The biodistribution, dosimetry, and safety of a new myocardial imaging agent, 99mTc-hexakis-2-methoxyisobutyl isonitrile (HEXAMIBI), was evaluated in 17 normal volunteers at rest and exercise (Phase I studies). Technetium-99m HEXAMIBI clears rapidly from the blood with good myocardial uptake and favorable myocardial-to-background ratios for myocardial imaging. Dosimetry allows for administration of up to 30 mCi (1, 110 Bq) of [99mTc]HEXAMIBI. The myocardial images were of good quality and appeared less granular with sharper myocardial walls compared to 201T1 images. The clinical efficacy of [99mTc]HEXAMIBI planar stress and rest imaging was evaluated in a multicenter Phase II clinical trial involving 38 patients. Of 36 patients with significant coronary artery disease, 35 patients (97%) had abnormal 201T1 stress images, and 32 (89%) had abnormal [99mTc]HEXAMIBI stress images (P = N.S.). Technetium-99m HEXAMIBI images correlated in 31/35 patients (86%) who had either scar or ischemia on 201T1 images. By segmental myocardial analysis, exact concordance was obtained in 463/570 myocardial segments (81%). This multicenter Phase I and II study indicates that planar [99mTc]HEXAMIBI stress imaging is safe and compares well with 201T1 stress imaging for detection of coronary artery disease.     

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.     

Pentavalent [99mTc]DMSA, [131I]MIBG, and [99mTc]MDP--an evaluation of three imaging techniques in patients with medullary carcinoma of the thyroid

Nine patients with histologically proven medullary carcinoma of the thyroid (MCT) were imaged using pentavalent [99mTc]dimercaptosuccinic acid [(V)DMSA], [131I] metaiodobenzylguanidine (MIBG) and [99mTc]methylene diphosphonate (MDP). Technetium-99m (V)DMSA demonstrated most of the tumor sites in eight patients with proven metastases, with an overall sensitivity of 95% in lesion detection. Iodine-131 MIBG showed definite uptake in some of the tumor sites in three of the nine patients imaged, with equivocal uptake seen in a further one patient, with sensitivity of only 11% for lesion detection. Technetium-99m MDP demonstrated bony metastases only, in four of the patients imaged yielding a sensitivity of 61%. Technetium-99m (V)DMSA has been demonstrated in this study to be a useful imaging agent in patients with MCT, showing uptake in significantly more lesions and with better imaging qualities than [131I]MIBG, and with the ability to detect soft tissue as well as bony metastases.     

Technetium-99m (99mTc) mercaptoacetyltriglycine: update on the new 99mTc renal tubular function agent.

Technetium-99m (99mTc) mercaptoacetyltriglycine (MAG3) is a new renal radiopharmaceutical that was recently introduced as a 99mTc-labeled replacement for iodine-131 (131I) o-iodohippurate (OIH). Since its introduction, a wide variety of in vitro and in vivo studies have been performed to characterize the high-performance liquid chromatography (HPLC)-purified complex and kit formulations. [99mTc]MAG3 has a slower plasma clearance, a higher plasma protein binding, less red blood cell (RBC) penetration, a lower extraction ratio, and a smaller volume of distribution than OIH. Because of the slower plasma clearance, [99mTc] MAG3 cannot be used as a direct measurement of effective renal plasma flow. Simplified methods have been developed to calculate [99mTc]MAG3 clearances, as well as regression equations to convert these clearances to an equivalent OIH value. The image quality of [99mTc]MAG3 is superior to [131I]OIH; the renogram curves and the fraction of the dose of the two agents that appears in the urine are almost identical, even though the plasma clearance of [99mTc]MAG3 is only 50% to 65% that of OIH. [99mTc]MAG3 compares favorably with OIH in patients with a wide range of clinical problems. The radiation dose to a patient with normal renal function using standard imaging doses is higher for [99mTc]MAG3 than for [131I]OIH, but in patients with impaired renal function, the radiation dose from [131I]OIH is much higher than [99mTc]MAG3. [99mTc]MAG3 also provides superior image quality compared with [99mTc]diethylenetriaminepentaacetic acid (DTPA) in patients with impaired renal function, but it is important to note that [99mTc]MAG3 cannot be used to measure the glomerular filtration rate (GFR). [99mTc]MAG3 is the most promising 99mTc tubular function agent to date, and it has replaced OIH and [99mTc]DPTA in a number of institutions. However, there are physiologic differences between these three agents and, therefore, they should not be expected to behave identically in all clinical conditions.     

Effect of reperfusion and hyperemia on the myocardial distribution of technetium-99m t-butylisonitrile

Technetium-99m t-butylisonitrile ([99mTc]TBI) is a promising new radiotracer for myocardial imaging. Its myocardial uptake is sufficiently high in humans to permit planar, tomographic, and gated images of excellent technical quality. We studied the behavior of [99mTc]TBI in the dog at rest and under conditions of hyperemia and reperfusion in order to determine the relationship between [99mTc]TBI myocardial concentration and blood flow. After permanent occlusion of the left anterior descending artery, the correlation between the relative myocardial concentration of [99mTc]TBI and regional myocardial blood flow (RMBF) measured with radiolabeled microspheres was excellent. In a dog model of transient hyperemia, the concentration of [99mTc]TBI was directly related to blood flow but underestimated the degree of hyperemia. Technetium-99m TBI redistributed into transiently ischemic myocardium. The myocardial concentrations of [99mTc]TBI and thallium-201(201TI) in transiently ischemic myocardium were similar at 10 and 30 min following reperfusion and were significantly higher than blood flow prior to reperfusion. When [99mTc]TBI was injected into the left anterior descending artery, the washout was slow, falling to 78% of initial activity at 120 min after injection. In conclusion, [99mTc]TBI reflects regional myocardial blood flow accurately in ischemic and normal resting myocardium and underestimates blood flow at high flows. The rate of myocardial redistribution after reperfusion is similar for [99mTc]TBI and 201TI.     

Popliteal cysts and deep venous thrombosis: Tc-99m red blood cell venography

Thirty-four patients who clinically were suspected of having deep venous thrombosis (DVT) underwent Tc-99m red blood cell (RBC) venography followed by contrast venography. The sensitivity (88%) and specificity (94%) of Tc-99m RBC venography for DVT confirmed findings of previous studies. Twenty-four patients who had proved popliteal cysts and swollen calves also were examined using Tc-99m RBC venography. Large cysts (greater than 9 X 4 X 4 cm) showed lack of DVT features, photon deficient cold areas in the popliteal fossa, and diversion of venous flow around the photon deficient area. These features were seen in 25% of the study population (six patients), and assisted in the distinction between the two conditions.     

Animal evaluation of technetium-99m triamide mercaptide complexes as potential renal imaging agents

Technetium-99m mercaptoacetylglycylglycylglycine (MAG3), a [99mTc]triamide mercaptide (N3S) compound has been synthesized in an attempt to obviate the stereochemistry problems associated with the diamide dimercaptide (N2S2) ligands. Because initial studies have been promising, the terminal glycine on the MAG3 compound has been varied to create a new series of N3S compounds. Twelve new N3S complexes were initially screened in mice and the more promising complexes, 99mTc mercaptoacetylgylcylglycyl-glycine [( 99mTc]MAG3), 99mTc mercaptoacetylgylcylglycyl-L-alanine [( 99mTc]MAG2-Ala), and both complexes of 99mTc mercaptoeacetylglycylglycyl-L-asparagine [( 99mTc]MAG2-Asn) and 99mTc mercaptoacetylglycylglycyl-L-glutamine [( 99mTc]MAG2-Gln), were further evaluated in rats utilizing constant infusion blood clearances, extraction efficiencies and protein binding assays. The renal excretion of all these complexes compared favorably with simultaneously administered [131I]OIH and [125I]iothalamate. The triamide mercaptide complexes represent a new ligand class for 99mTc, which may provide a variety of complexes for the evaluation of renal tubular function.     

Simultaneous assessment of left ventricular wall motion and myocardial perfusion with technetium-99m-methoxy isobutyl isonitrile at stress and rest in patients with angina: comparison with thallium-201 SPECT

The newly developed technetium-99m (99mTc) isonitriles can be used for the simultaneous evaluation of ventricular function and myocardial perfusion. We compared technetium-99m hexakis-2-methoxy isobutyl isonitrile [( 99mTc] MIBI) derived first-pass left ventricular wall motion at stress and rest with simultaneous myocardial perfusion defined by [99mTc]MIBI SPECT. These results were then compared with 201TI SPECT. We examined 28 patients with coronary artery disease; 25 had a previous myocardial infarction. We found concordance between segmental wall motion and myocardial perfusion imaging in defining normal, ischemic, and infarcted myocardium in 68% and 69% of segments using [99mTc]MIBI and 201TI respectively. The best agreement between wall motion and myocardial perfusion was seen in the inferior wall, while most of the discrepancies were found at the apex. Agreement between [99mTc]MIBI and 201TI SPECT myocardial perfusion was seen in 93% of segments. Technetium-99m-MIBI appears to be an ideal radiopharmaceutical for the simultaneous evaluation of ventricular function and myocardial perfusion during stress and at rest.     

Comparison of technetium-99m MAG3 kit with HPLC-purified technetium-99m MAG3 and OIH in rats

Technetium-99m (99mTc) mercaptoacetylglycylglycylyglycine (MAG3) in high (greater than or equal to 95%) radiochemical purity is prepared from lyophilized kits containing benzoylMAG3, sodium tartrate, lactose, and stannous chloride by adding sodium [99mTC]pertechnetate and heating the contents briefly. Constant-infusion renal whole-blood clearance obtained with [99mTc] MAG3 kits was compared with that obtained with high performance liquid chromatography (HPLC) pure [99mTc]MAG3 and with co-infused iodine-131 (131I) iodohippurate (OIH) in anesthetized rats. Average renal whole-blood clearance of [99mTc]MAG3 from kits was 3.9 +/- 0.4 ml/min/100 g body weight (mean +/- s.e.m. n = 5) and that for HPLC-pure [99mTc]MAG3 was 4.6 +/- 0.3 (n = 3). Renal whole-blood clearance ratios for [99mTc]MAG3 to co-infused iodine-131 (131I) OIH were greater than unity for both kit formulation (1.7 +/- 0.1) and HPLC-pure [99mTc]MAG3 (1.9 +/- 0.2). Differences in these two measures were not significant. Plasma binding (determined from blood drawn at the end of the infusion) of [99mTc]MAG3 prepared from both kits (75 +/- 2%, n = 4) and HPLC-separation (76 +/- 4%) were greater than that of [131I]OIH in corresponding plasma samples (31 +/- 1% and 32 +/- 2%) respectively). Renograms performed in anesthetized rats revealed no statistically significant differences between kit-prepared [99mTc]MAG3 and [131I]OIH in terms of time-to-peak renal activity (5.0 +/- 1.7 min, n = 6; and 2.2 +/- 0.2 min, n = 3, mean +/- s.e.m. for [99mTc]MAG3 and [131I]OIH, respectively), in terms of time to fall to half-maximal activity (15.3 +/- 2.4 min and 9.6 +/- 2.1 min, respectively), or in terms of fraction of peak radioactivity in right kidney (0.53 +/- 0.01 for both substances). To assess possible interference from hepatobiliary uptake and excretion in renal failure, radioactivity in liver regions of interest was followed by gamma camera scintigraphy for 30 min after intravenous injection of [131I]OIH and kit and HPLC-purified [99mTc]MAG3 in anesthetized rats rendered anephric by ligating renal peduncles. Liver activity was 25% of total for both preparations of [99mTc]MAG3 and was 22% of total for [131I]OIH. There were no significant differences among the substances.     

Technetium-99m red blood cell venography of the lower limb in symptomatic pulmonary embolization

Tc-99m RBC venography of the legs was obtained in 42 patients with primary pulmonary symptomatology and a diagnosis of pulmonary embolization. In 31 of these 42 patients (74%), the nuclear venogram revealed the presence of deep vein thrombosis (DVT) and a source of embolization. Of the 31 patients with leg DVT documented by venography, 13 (42%) showed thrombosis confined to the calf. Clinical findings suggested that only 20 of the 31 patients (65%) with DVT could have harboured a source of embolization in the legs. Tc-99m RBC venography is a useful noninvasive test for the global and comprehensive assessment of patients with symptomatic pulmonary embolization.     

Comparison of technetium-99m pyrophosphate and technetium-99m DTPA aerosols for SPECT ventilation lung imaging

Although [99mTc] diethylenetriaminepentaacetic acid (DTPA) is currently the most widely used radioaerosol, rapid alveolar clearance limits its usefulness for single photon emission computed tomography (SPECT) ventilation lung imaging. Previous research has shown that [99mTc]phosphate compounds have high alveolar deposition and slow clearance and thus provide suitable aerosols for pulmonary ventilation studies. We have compared the pulmonary retention and blood levels of [99mTc]pyrophosphate (PYP) and [99mTc]DTPA in eight normal nonsmoking male volunteers. These two radioaerosols have comparable pulmonary deposition. Technetium-99m PYP, however, has a much slower pulmonary clearance which allows sufficient time (20 or more minutes) for SPECT data acquisition using a single-headed rotating gamma camera. While the radiation absorbed dose to the lungs for [99mTc]PYP (0.31 rad/mCi) is greater than for [99mTc]DTPA (0.11 rad/mCi), it is at a clinically acceptable and safe level.     

Technetium-99m MAG-3 clearances after captopril in experimental renovascular hypertension

Rats with one kidney clamped (2K1C), both kidneys clamped (2K2C), unilaterally nephrectomized with remaining kidney clamped (1K1C), and normals, were studied using 99mTc mercaptoacetyltriglycine ([ 99mTc]MAG-3) and 131I orthoiodohippurate ([131I]OIH). Clearances of [99mTc]MAG-3 and [131I]OIH were performed after constricted rats became hypertensive. Clearances were repeated after i.v. Captopril. Clearances of [99mTc]MAG-3 and [131I]OIH in normals didn't change significantly after Captopril. Clearances of [99mTc]MAG-3 and [131I]OIH decreased insignificantly after Captopril in the 2K2C model. in the 2K1C group, normal kidney clearance increased ([99mTc]MAG-3 p less than 0.01 and [131I]OIH p less than 0.025) and clamped kidney clearance decreased after inhibition ([99mTc]MAG-3, p less than 0.01, [131I]OIH p less than 0.02). Clearances increased in the 1K1C group after Captopril ([99mTc]MAG-3 p less than 0.0025 and [131I]OIH, p less than 0.001). The ratio of [99mTc]MAG-3 to [131I]OIH before Captopril was 0.81 and 0.84 after Captopril. Changes in renal function after Captopril depend on the model of renovascular hypertension and possibly the dose administered. Technetium-99m MAG-3 clearance parallels [131I]orthoiodohippurate in renovascular hypertension.     

Deep vein thrombosis: significant limitations of noninvasive tests

Impedance plethysmography (IPG) has a reputed sensitivity of 95% in the detection of proximal, clinically significant deep venous thrombosis (DVT). A review of the radiologic studies of 100 consecutive patients who underwent both venography and IPG showed venographic evidence of proximal DVT in 40 patients. The IPG was negative in 15 (38%) of these 40 cases. The specificity of the IPG was 83%. The predictive value of a negative study, with this 40% prevalence of DVT, was 77%. These disturbing results indicate a continuing role for venography in the workup of DVT.     

Uptake of myocardial imaging agents by rejecting and nonrejecting cardiac transplants. A comparative clinical study of thallium-201, technetium-99m, and gallium-67

To study the scintigraphic detectability of cardiac rejection, we performed 135 planar myocardial scans ([99mTc]pyrophosphate, 85; 201Tl, 36; 67Ga, 14) together with endomyocardial biopsies in ten patients for a (mean) 17-mo postoperative period. Specificity of each agent exceeded 89%. Technetium-99m pyrophosphate showed results that significantly correlated with the severity of rejection (p = 0.03), as shown by biopsy, but neither 201Tl nor 67Ga did so (p = 0.63 and 0.81, respectively). Technetium-99m pyrophosphate showed better diagnostic accuracy (85%) than 201Tl (69%) and 67Ga (64%). Technetium-99m pyrophosphate also showed higher negative predictive value (91%) than thallium (76%) and gallium (69%). Thus, a normal 99mTc pyrophosphate scan was usually associated with absence of cardiac rejection. However, all three agents showed unacceptably poor sensitivity (0% to 30%) and thus were not useful as a screening test for cardiac rejection, even when the same agent was used serially in imaging a given patient.     

Cardiac blood-pool scintigraphy using technetium-99m DTPA-HSA: comparison with in vivo technetium-99m RBC labeling

We performed cardiac blood-pool scintigraphy using technetium-99m diethylenetriaminepentaacetic acid human serum albumin [( 99mTc] DTPA-HSA), a newly developed blood-pool agent, in 31 patients with various heart diseases and evaluated its clinical usefulness in comparison with the conventional in vivo 99mTc red blood cell (RBC) labeling. Excellent cardiac blood-pool images were obtained by [99mTc]DTPA-HSA method. Biodistribution studies showed higher accumulation of [99mTc]DTPA-HSA than that of 99mTc RBC in the lungs and liver, but similar count ratios of the cardiovascular blood pool to whole body between the two methods. In ECG-gated end-diastolic images, no quantitatively significant difference was observed in left ventricular target-to-background ratios between these two methods. Left ventricular ejection fraction (LVEF) calculated by [99mTc]DTPA-HSA MUGA method was correlated well with that by contrast LVEF (r = 0.91). No side effects were observed in any patient. In conclusion, cardiac blood-pool scintigraphy using [99mTc] DTPA-HSA is readily performed by single i.v. injection and useful for the assessment of cardiac function.     

Dynamic SPECT with technetium-99m HM-PAO in meningiomas--a comparison with iodine-123 IMP

Technetium-99m hexamethylpropyleneamine oxime ([99mTc]HM-PAO) has recently been introduced as an alternative to N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) for measurement of regional cerebral blood flow. This study compares dynamic SPECT studies using the two tracers in seven patients with meningiomas. Regions of interest were placed over the lesion and contralateral homologous presumed normal area. The counting-rate ratio for the lesion to the contralateral homologous area (L/N ratio) was then calculated in the first image. L/N ratios of [99mTc]HM-PAO single photon emission computed tomography (SPECT) were lower than those of [123I])IMP SPECT, particularly in hypervascular meningiomas. Furthermore, time-activity curves showed that the washout of [99mTc]HM-PAO in the tumors was very slow or incomplete, preventing an accurate assessment of vascularity of meningiomas with [99mTc]HM-PAO, as is generally possible with [123I]IMP.     

Characterization of technetium-99m-L,L-ECD for brain perfusion imaging, Part 1: Pharmacology of technetium-99m ECD in nonhuman primates

Technetium-99m ethyl cysteinate dimer ([99mTc]ECD) is a neutral, lipophilic complex which rapidly crosses the blood-brain barrier. Brain retention and tissue metabolism of [99mTc]ECD is dependent upon the stereochemical configuration of the complex. While both L,L and D,D enantiomers are extracted by the brain, only the L,L but not the D,D form, is metabolized and retained in the monkey brain (4.7% injected dose initially, T 1/2 greater than 24 hr). Dynamic single photon emission computed tomography imaging studies in one monkey indicates 99mTc-L,L-ECD to be distributed in a pattern consistent with regional cerebral blood flow for up to 16 hr postinjection. Dual-labeled 99mTc-L,L-ECD and [14C]iodoantipyrine autoradiography studies performed 1 hr after administration show cortical gray to white matter ratios of both isotopes to be equivalent (approximately 4-5:1). These data suggest that 99mTc-L,L-ECD will be useful for the scintigraphic assessment of cerebral perfusion in humans.     

Mechanism of renal concentration of technetium-99m glucoheptonate

Seventy female Sprague-Dawley rats were studied to determine the mechanism of tubular localization and the effects of commonly encountered changes in hydration and acid-base balance on renal uptake and urinary excretion of technetium-99m glucoheptonate ([99mTc]GHA). The in-vivo protein binding and protein-free plasma clearance of [99mTc]GHA also were quantitated. Twenty additional rats were studied to determine the effects of PAH competition and probenecid blockade on renal uptake of [99mTc]dimercaptosuccinic acid (DMSA) in comparison with their effects on [99mTc]GHA localization. Kidney uptake of [99mTc]GHA averaged 11.17 +/- 0.49 (s.e.)% of the injected dose in control animals. This varied slightly among groups but was significantly reduced by probenecid blockade and para-aminohippuric acid (PAH) competition to 4.08 +/- 0.55 (p less than 0.005) and 2.39 +/- 0.14 (p less than 0.005), respectively. Technetium-99m DMSA was not affected in its renal accumulation by these maneuvers. The total plasma clearance of [99mTc]GHA was lower than iodine-125(125I)iothalamate but the clearance of the protein free supernate was higher, raising a possibility of some tubular secretion. Acidification of the urine which has been shown to reduce [99mTc]DMSA uptake appeared to have no effect on [99mTc]GHA. Hepatic uptake was minimal in all groups averaging less than 1% injected dose. These data demonstrate that renal accumulation of [99mTc]GHA is blocked by probenecid and PAH suggesting that it is actively concentrated in the proximal tubule by enzyme systems similar to those involved in PAH and hippuran transport. It appears that [99mTc]GHA uptake measures a different aspect of kidney function than [99mTc]DMSA.