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Technetium-99m-HMPAO, technetium-99m-ECD and iodine-123-IMP cerebral blood flow measurements with pharmacological interventions in primates.

UNLABELLED: Technetium-99m-bicisate ethyl cysteinate dimer (ECD) presents a different pattern from cerebral blood flow (CBF) in the subacute phase of cerebral infarction, as measured by PET, perhaps due to lack of oxygen and enzyme activity; this pattern is contrary to that of hexamethyl-propyleneamine oxime (HMPAO) but similar to that of N-isopropyl-[123I]beta-iodoamphetamine ([123I]IMP). This study explores possible CBF differences among HMPAO, ECD and IMP, with various relevant drug interventions. METHODS: Anesthetized adult baboons were used in these SPECT studies. Four studies (n = 6 baboons for each study), one control study and three intervention studies involving intravenous acetazolamide, nimodipine infusion and intramuscular sumatriptan, were followed with 99mTc-HMPAO, 99mTc-ECD and [123I]IMP. The split-dose method was used as follows. For each tracer, intervention data from the second SPECT (SPECT-2) after the second tracer injection (444 MBq) reflected a change in CBF with respect to the baseline SPECT (SPECT-1) data from the initial injection (222 MBq). These changes as a ratio, R (R = SPECT-2/SPECT-1), for each study, and the R values for each tracer were compared to R values from the corresponding control studies, yielding a quantitative estimate of drug effects. RESULTS: There were no significant differences (p > 0.05) between HMPAO and ECD for the control, acetazolamide and sumatriptan studies, but there was indeed a difference between the two for the nimodipine study, indicating a nimodipine-dependent underestimation of CBF with ECD (and also with IMP), with respect to HMPAO. A further significant difference was that larger CBF increases were observed with acetazolamide, as measured with [123I]IMP. CONCLUSION: This is a crucial observation for the clinical interpretation of CBF SPECT data and should direct the choice of tracer for a specific examination.

Acetazolamide↗

Discordance of technetium-99m-HMPAO and technetium-99m-ECD SPECT in herpes simplex encephalitis.

UNLABELLED: Technetium-99m-hexamethyl propyleneamine oxime (HMPAO) and 99mTc-ethyl cysteinate dimer (ECD) accumulate in brain tissue in proportion to regional cerebral blood flow in healthy subjects and in patients with a variety of neurological diseases. We report on four patients with herpes simplex encephalitis and the discordance between these two approved cerebral perfusion imaging radiopharmaceuticals. CONCLUSION: SPECT images showed unilateral regional increase of 99mTc-HMPAO uptake and decrease of 99mTc-ECD uptake in the affected temporal lobe.

Brain↗

Reduced variability of interpretation and improved image quality with a technetium 99m myocardial perfusion agent: comparison of thallium 201 and technetium 99m-labeled tetrofosmin.

BACKGROUND: The purpose of this study was to determine the relative image quality and interobserver variability among four readers for 201Tl and 99mTc-labeled tetrofosmin myocardial perfusion images. 99mTc-labeled perfusion agents, with near-optimal physical characteristics for gamma camera imaging, may allow for superior image quality and improved consistency of interpretation. However, most studies to date have demonstrated only similarity in the diagnostic accuracy between technetium agents and thallium. Tetrofosmin is a recently developed 99mTc-labeled agent that has shown promising results in early clinical trials. METHODS AND RESULTS: A multicenter, open-label trial was performed during which treadmill exercise thallium and tetrofosmin scintigraphy was performed within a 2-week period of each other in 216 subjects. Image quality was evaluated subjectively and scans were interpreted in a blinded, independent fashion by four readers. Perfusion abnormalities were graded as consistent with ischemia, infarction, or mixed and were described both globally and regionally. Interobserver variability was assessed by use of the kappa statistic, and receiver-operator curves were compared for each observer for the diagnostic accuracy of each agent. More tetrofosmin images were of excellent quality than with thallium (52% vs 28%; p < 0.05), and when differences in quality were noted between the agents, tetrofosmin was more often superior (p < 0.0001). The interobserver variability was lower with tetrofosmin scintigraphy because generally higher kappa values were noted, especially in the lateral wall. Higher receiver-operator curve areas indicative of improved diagnostic accuracy were noted among the four readers for tetrofosmin in 80% of vascular territories. CONCLUSIONS: 99mTc-labeled tetrofosmin scintigraphy yields images of improved quality compared with thallium, and there is an overall improvement in the consistency of image analysis associated with the use of tetrofosmin.

Coronary Disease↗

Microwave-assisted sample treatment in a fully automated flow-based instrument: oxidation of reduced technetium species in the analysis of total technetium-99 in caustic aged nuclear waste samples.

An automated flow-based instrument for microwave-assisted treatment of liquid samples has been developed and characterized. The instrument utilizes a flow-through reaction vessel design that facilitates the addition of multiple reagents during sample treatment and removal of the gaseous reaction products and enables quantitative removal of liquids from the reaction vessel for carryover-free operations. Matrix modification and speciation control chemistries that are required for the radiochemical determination of total (99)Tc in caustic aged nuclear waste samples have been investigated. A rapid and quantitative oxidation procedure using peroxydisulfate in acidic solution was developed to convert reduced technetium species to pertechnetate in samples with high content of reducing organics. The effectiveness of the automated sample treatment procedures has been validated in the radiochemical analysis of total (99)Tc in caustic aged nuclear waste matrixes from the Hanford site.

Journal Article↗

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.

Animals↗

Comparison of technetium-99m pyrophosphate and technetium-99m methylene diphosphonate with variable amounts of stannous chloride in the detection of acute myocardial infarction.

The authors prospectively compared the ability of Tc-99m pyrophosphate (PYP) and Tc-99m methylene diphosphonate (MDP) to detect acute myocardial infarctions. The agents used were PYP (12 mg) with 3.4 mg of stannous chloride, MDP (10 mg) with 1.0 mg of stannous chloride, and MDP (10 mg) with 3.4 mg of stannous chloride. Imaging was performed on three consecutive days on 34 patients with proven myocardial infarctions, using the same agent on the first and third days of the study and an alternate agent on the second day. Agents were assigned randomly to each of six groups of patients. First images were obtained an average of 3.7 days (range, one to six days) following myocardial infarction. Seventeen of 23 patients (75%) had images positive for acute myocardial infarction with Tc-99m PYP, whereas only two of 21 patients (9.5%) had positive studies with Tc-99m MDP with 3.4 mg of stannous chloride and one of 24 patients (4.2%) had positive studies with Tc-99m MDP and 1.0 mg of stannous chloride. All three myocardial infarctions detected by Tc-99m MDP were extensive and transmural. When MDP and PYP were both positive in the same patient, the apparent size of the myocardial infarction was much smaller with the MDP. It is concluded that MDP can detect only large myocardial infarctions, has poor localization in the infarcted tissue, and varying the stannous chloride content of the preparation does not improve the ability of MDP to detect acute myocardial infarctions.

Adult↗

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.

Adult↗

Using the "integral spleen" method of radiorenogram analysis and a baboon model to compare the diagnostic usefulness of technetium-99m-diethylenetriamine pentaacetic acid to that of various technetium-99m-mercaptoacetyltriglycene formulations and iodine-123-hippuran.

In light of the high price of commercially available mercaptoacetyltriglycene (MAG3) it was decided to attempt a local MAG3-formation and to test this against diethylenetriamine pentaacetic acid (DTPA), 123I-Hippuran, and commercial MAG3 for diagnostic radiorenographic capabilities also in conjunction with furosemide and captopril. A baboon model (n = 6) was used, and the parameters evaluated were obtained by the "integral spleen" method of radiorenogram analysis. Although the images and parameters pointed to 123I-Hippuran and commercial MAG3 as the ideal renal scanning agents and to DTPA as the least so, with the local product an acceptable alternative, the differences were not significant enough to warrant either the purchase of the commercial product or the extensive development of the local product. Inexpensive 99mTc-DTPA in conjunction with modern computer techniques will probably supply most of the answers.

Animals↗

Comparison of technetium-99m sulfur colloid and in vitro labeled technetium-99m RBCs in the detection of gastrointestinal bleeding.

Twenty-seven paired Tc-99m sulfur colloid (SC) and Tc-99m RBC studies were evaluated for the detection of GI bleeding. The only two positive Tc-99m SC studies had positive early Tc-99m RBC studies as well. There were 15 other positive Tc-99m RBC studies (three during the first hour) and these were associated with normal Tc-99m SC scans. Approximately 70% of the positive Tc-99m RBC studies occurred after 1 hour. Tc-99m RBCs should be the initial test in patients with GI bleeding.

Adolescent↗

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.

Alanine↗

Technetium-99m MDP vs technetium-99m dicarboxypropane diphosphonate. A clinical comparison in various pathologic conditions.

The performance of Tc-99m MDP vs Tc-99m dicarboxypropane diphosphonate (DPD) was evaluated in 20 patients with various skeletal bone diseases. Each patient was investigated twice, with an interval of three days between studies and using the same protocol, hence each case served as its own control. The results were: In a subjective interpretation by five independent and experienced investigators, the difference between agents was small, yet in favor of MDP. Region of interest (ROI) analysis of the pooled results in 74.4% of all cases shows a higher bone lesion to normal bone ratio (BL/NB), and in 79.3% of all cases, a better bone lesion to soft tissue ratio (BL/ST) with Tc-99m MDP. When considering pathology types separately, the BL/NB ratio of Tc-99m MDP was 17.7% higher than the one of Tc-99m DPD in metastases, 9.5% higher in rheumatoid arthritis, 2.8% higher in metabolic diseases, and 24% higher in bone fractures. Student's paired t test on the pooled BL/NB ratios shows a difference of 15.5% for Tc-99m MDP, significant at P = 0.00155. The overall results of our study favor Tc-99m MDP.

Adult↗

Images of liposarcoma using technetium-99m bleomycin and technetium (V)-99m DMSA.

The effectiveness of Tc-99m bleomycin (BLM) and Tc(V)-99m DMSA are compared with that of Ga-67 citrate, which is currently the most widely used agent. In four patients with lipomatous tumors, the clinical significance of tumor imaging with each of these three agents is discussed and compared. Results indicate that both Tc-99m BLM and Tc(V)-99m DMSA are superior in detecting the extension or localization of liposarcomas.

Adult↗

Comparison of technetium-99m sulfur colloid and technetium-99m albumin colloid labeled solid meals for gastric emptying studies.

A Tc-99m albumin colloid (Tc-AC) kit has been introduced as an alternative to Tc-99m sulfur colloid (Tc-SC) for liver-spleen imaging. Since there is no need for boiling, the use of Tc-AC reduces preparation time and manipulation. Tc-SC is one of the most commonly used radiopharmaceuticals for the labeling of solid-phase markers in gastric emptying studies. In vitro studies were performed to evaluate the labeling efficiency and stability in hydrochloric acid and in human gastric juice of intracellularly labeled chicken liver and scrambled eggs labeled with Tc-SC and Tc-AC. Gastric emptying studies also were performed on 20 healthy volunteers with both Tc-SC and Tc-AC labeled scrambled egg sandwiches. There was no significant difference between Tc-SC and Tc-AC in the labeling efficiency of chicken liver (98% +/- 1% for Tc-SC, 96% +/- 2% for Tc-AC) and scrambled eggs (92% +/- 2% for Tc-SC, 91% +/- 3% for Tc-AC). However, both Tc-SC and Tc-AC labeled scrambled eggs showed a lower stability than chicken liver, particularly in human gastric juice. Gastric emptying curves from both meals in 20 normal subjects were also similar, with a mean half-emptying time of 85 +/- 13 minutes and 87 +/- 16 minutes for the meals containing Tc-SC and Tc-AC respectively. Tc-AC is a reliable alternative to Tc-SC as a radiotracer for solid-phase gastric emptying studies.

Adult↗

Discordant uptake of technetium-99m DISIDA and technetium-99m sulfur colloid in an amebic abscess.

Hepatobiliary imaging in a patient with an amebic abscess showed an early cold defect that later showed rim enhancement. A Tc-99m SC scan did not show prominent flow (making hepatoma unlikely) and showed the previously noted defect to appear larger and without rim enhancement. The differential damage to Kupffer cells and hepatocytes or edema may account for these findings. Amebic abscess should be included in the differential diagnosis of lesions that give increased Tc-99m IDA but cold Tc-99m SC images.

Adult↗