Estimation of myocardial perfusion and viability using simultaneous 99mTc-tetrofosmin--FDG collimated SPECT.
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This study was designed to elucidate the usefulness of crosstalk correction for dual-isotope simultaneous acquisition (DISA) with 99mTc-tetrofosmin and FDG in estimating myocardial perfusion and viability. METHODS: Eighteen patients with coronary artery disease were studied. First, SPECT was performed with a low-energy high-resolution collimator after a single injection of 99mTc-tetrofosmin (single 99mTc-tetrofosmin). Second, PET and DISA with an ultra-high-energy collimator were performed after glucose loading and an injection of FDG. DISA was designed to operate with simultaneous 3-channel acquisition, and weighted scatter correction of crosstalk from the 18F photopeak to the 99mTc photopeak was performed by modification of an existing dual-window technique. The FDG SPECT images were compared with the images obtained by PET. Both crosstalk-corrected and uncorrected 99mTc-tetrofosmin images were generated and compared with the single 99mTc-tetrofosmin images. RESULTS: Regional percentage uptake of FDG agreed well between DISA and PET. However, regional percentage uptake of 99mTc-tetrofosmin was generally higher on the uncorrected 99mTc-tetrofosmin images than on the single 99mTc-tetrofosmin images, especially in areas of low flow (percentage count of 99mTc-tetrofosmin > or = 50%). The crosstalk correction contributed to improving the agreement between regional percentage uptakes and significantly improved the detectability of myocardial perfusion-metabolism mismatching. CONCLUSION: With 3-channel acquisition and weighted-scatter correction of crosstalk from the 18F photopeak to the 99mTc photopeak, DISA with 99mTc-tetrofosmin and FDG is feasible for assessing regional myocardial perfusion and viability. (+info)
The effects of circulating antigen on the pharmacokinetics and radioimmunoscintigraphic properties of 99m Tc labelled monoclonal antibodies in cancer patients.
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PURPOSE. This article reports the pharmacokinetics, radiation dosimetry and radioimmunoscintigraphy (RIS) of two (99m)Tc-labelled monoclonal antibodies (MAb) used to detect cancer. METHODS: The effects of circulating antigen in female cancer patients are explored and their effects on the ability of these MAbs to effectively perform as RIS agents noted. To illustrate the effects of circulating antigen, data using MAb B43.13 (OVAREX, AltaRex Corp., Waltham, MA, USA) from a Pilot study in ovarian cancer patients are presented. The results from a Phase II study of MAb 170H.82 (Tru-Scint AD, BIOMIRA INC., Edmonton, Alberta, Canada) in patients with primary and locally recurrent breast cancer were used to portray the biodistribution patterns when no circulating antigen is present. Data from planar gamma camera images were obtained for both groups and used for pharmacokinetic and radiation dosimetry analyses. RESULTS: A pharmacokinetic analysis indicated a shorter residence time and higher clearance of (99m)Tc-MAb-B43.13 that was ascribed in part to the circulating CA 125 antigen in this group of ovarian cancer patients. CONCLUSION: These clearance patterns resulted in acceptable, though higher radiation doses to the spleen and urinary bladder wall for these patients when compared to the MAb-170H.82 group. Both MAbs were found to produce acceptable radioimmunoscintigraphic images (+info)
Scintigraphic imaging of the hypoxia marker (99m)technetium-labeled 2,2'-(1,4-diaminobutane)bis(2-methyl-3-butanone) dioxime (99mTc-labeled HL-91; prognox): noninvasive detection of tumor response to the antivascular agent 5,6-dimethylxanthenone-4-acetic acid.
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5,6-Dimethylxanthenone-4-acetic acid (DMXAA) and combretastatin A4 phosphate (CA-4-P) markedly inhibit tumor blood flow in mice and are both currently in clinical trial. One of the challenges in clinical evaluation of antivascular agents is the monitoring of tumor blood flow inhibition in individual patients. This study investigates, using mouse models, whether a new marker for tissue hypoxia, (99m)technetium-labeled 2,2'-(1,4-diaminobutane)bis(2-methyl-3-butanone) dioxime (99mTc-labeled HL-91; Prognox)] has potential for the scintigraphic monitoring of tumor response to antivascular agents. Determination of radioactivity in dissected tissues 3 h after DMXAA (80 micromol/kg) or CA-4-P (227 micromol/kg) was injected indicated that both drugs inhibited blood flow (86RbCl uptake; 84 and 87%, respectively) and increased 99mTc-labeled HL-91 levels (350 and 300%, respectively) selectively in murine RIF-1 tumors. Planar imaging of 99mTc-labeled HL-91 3 h after DMXAA injection showed a dose-dependent increase in tumor levels above a threshold of 50 micromol/kg; this same threshold was observed for the inhibition of tumor blood flow (determined using Hoechst 33342). DMXAA also inhibited blood flow--and increased 99mTc-labeled HL-91 uptake--in MDAH-MCa-4 mouse mammary carcinomas and in NZMN10 human melanoma xenografts. Whether 99mTc-labeled HL-91 might also be useful as a biomarker for tumor cell killing was investigated by clonogenic assay of surviving cells 15 h after imaging 99mTc-labeled HL-91 in RIF-1 tumors. Log cell kill in individual tumors showed a statistically significant linear correlation (P < 0.001) with 99mTc-labeled HL-91 uptake after 60 micromol/kg (r2 = 0.79) and 70 micromol/kg (r2 = 0.44) but not at 80 micromol/kg DMXAA. The lack of correlation at high doses presumably reflects the insensitivity of the tumor-averaged 99mTc-labeled HL-91 signal to small regions in which tumor blood flow is preserved (which will limit log cell kill). The results indicate the potential of 99mTc-labeled HL-91 for the noninvasive imaging of tumor blood flow inhibition by antivascular drugs in humans. (+info)
Quantitative measurement of cerebral blood flow by (99m)Tc-HMPAO SPECT in acute ischaemic stroke: usefulness in determining therapeutic options.
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OBJECTIVE: Early recanalisation by thrombolysis is a conclusive therapy for acute ischaemic stroke. But this therapy may increase the risk of intracerebral haemorrhage or severe brain oedema. The purpose was to evaluate usefulness of quantitative measurement of cerebral blood flow by single photon emission computed tomography (SPECT) in predicting the risk of haemorrhage or oedema, and determining the therapeutic options in acute hemispheric ischaemic stroke. METHODS: The relation was studied retrospectively between initial regional cerebral blood flow (rCBF) quantitatively measured by technetium-99m-labelled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) SPECT and final clinical and radiological outcome in 20 patients who presented hemispheric ischaemic stroke and were treated conservatively or received early recanalisation by local intra-arterial thrombolysis. The non-invasive Patlak plot method was used for quantitative measurement of rCBF by SPECT. RESULTS: Regions where residual rCBF was preserved over 35 ml/100 g/min had a low possibility of infarction without recanalisation and regions where residual rCBF was preserved over 25 ml/100 g/min could be recovered by early recanalisation. However, regions where residual rCBF was severely decreased (< 20 ml/100 g/min) had a risk of intracerebral haemorrhage and severe oedema. CONCLUSIONS: A quantitative assessment of residual rCBF by (99m)Tc-HMPAO SPECT is useful in predicting the risk of haemorrhage or severe oedema in acute ischaemic stroke. Therapeutic options should be determined based on the results of rCBF measurement. (+info)
Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1.
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The renal tubular secretion of thiazides and loop diuretics via the organic anion transport system in renal tubules is required for them to reach their principal sites of action. Similarly, acetazolamide, a diuretic clinically administered for glaucoma, is excreted from the kidney by glomerular filtration and tubular secretion. In this study, we investigated the interaction and transport of these diuretics via the rat renal organic anion transporter rOAT1 by using Xenopus laevis oocyte expression system. p-[(14)C]Aminohippurate (PAH) uptake by rOAT1-expressing oocytes was inhibited in the presence of a thiazide (chlorothiazide, cyclothiazide, hydrochlorothiazide), a loop diuretic (bumetanide, ethacrynic acid, furosemide), or a carbonic anhydrase inhibitor (acetazolamide, ethoxzolamide, methazolamide). Dixon plot analysis demonstrated that the inhibition constant (K(i)) value was 1.1 mM for acetazolamide, 150 microM for hydrochlorothiazide, 9.5 microM for furosemide, and 5. 5 microM for bumetanide. Kinetic analysis revealed that acetazolamide inhibited rOAT1 competitively and that inhibition style of furosemide was a mixture of competitive and noncompetitive. [(14)C]PAH efflux was significantly enhanced when the rOAT1-expressing oocytes were incubated in the presence of unlabeled PAH, alpha-ketoglutarate, acetazolamide, chlorothiazide, or hydrochlorothiazide. rOAT1 stimulated acetazolamide uptake, which was inhibited by probenecid. Although the loop diuretics had little trans-stimulation effect on [(14)C]PAH efflux via rOAT1, the rOAT1-mediated furosemide uptake was observed. These findings suggest that rOAT1 contributes, at least in part, to the renal tubular secretion of acetazolamide, thiazides, and loop diuretics. (+info)
Normal patterns on 99mTc-ECD brain SPECT scans in adults.
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Normative ethyl cysteinate dimer (ECD) SPECT data must be available to successfully apply ECD SPECT to clinical studies. The purpose of this study was to determine ECD SPECT scan patterns of healthy adults. METHODS: Forty-eight healthy volunteers (22 men, 26 women; age range, 22-95 y; mean age, 47.6 +/- 19.2 y) underwent high-resolution ECD SPECT. For visual analysis of regional brain ECD uptake, we used a scale of +3 to -3, in which +3 and -3 indicated highest ECD uptake and deficit, respectively. For quantitative analysis, we measured the region-to-cerebellum ratio (R/CE) and the region-to-cerebral cortex ratio (R/CO) for 17 regions (13 cortical, 3 subcortical, and 1 cerebellar). RESULTS: On visual analysis, no subject had a score of -3. All subjects had a score of -2 for the hippocampus and a score of +3 for the medial occipital cortex, except for 2 subjects who had a score of +3 for the striatum and thalamus. A frontal eye field and posterior parieto-occipital junction were identified in 60% of subjects with a score of +1 and 79% of subjects with a score of +2. On quantitative analysis, a significant regional variation (ANOVA, P < 0.0001) was seen in R/CE, ranging from 0.709 (hippocampus) to 1.26 (medial occipital cortex). However, regional right-to-left differences and intersubject variability of R/CE were small (asymmetry index, 3.6% +/- 0.8%; coefficient variation, 6.6% +/- 0.7%). R/CE declined significantly with age in 6 regions, including the anterior and posterior cingulate cortex, superior prefrontal and parietal cortex, striatum, and hippocampus (1.0%-2.0% per decade, P < 0.05), whereas R/CO in the cerebellum increased significantly with age (1.0% per decade, P < 0.05). CONCLUSION: Although regional ECD brain perfusion patterns vary significantly, including variability caused by the age-related effect, intersubject variability is small. Recognition of these normal patterns is important for clinical interpretation of ECD SPECT studies. (+info)
Uptake of 99mTc-MIBI and 99mTc-tetrofosmin into malignant versus nonmalignant breast cell lines.
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The kinetics and cellular uptake of 99mTc-2-hexakis 2-methoxyiso-butyl-isonitrile (MIBI) and 99mTc-1 ,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) into malignant versus nonmalignant human breast cell lines were investigated and compared. METHODS: At specific intervals after incubation at 37 degrees C and 22 degrees C with 99mTc-MIBI or 99mTc-tetrofosmin, the uptake characteristics of radiotracers into human adenocarcinoma breast cell lines MCF-7 and SK-BR-3 and human breast, nontumor cell line HBL-100 were assessed. RESULTS: The uptake of 99mTc-MIBI and 99mTc-tetrofosmin was lower at an incubation temperature of 22 degrees C than that at 37 degrees C in the 3 cell lines. In MCF-7 and in SK-BR-3 cells the uptake of 99mTc-MIBI was significantly higher than the uptake of 99mTc-tetrofosmin. The uptake of 99mTc-MIBI was significantly higher into MCF-7 and SK-BR-3 cells than that into HBL-100 cells. In comparison with HBL-100 cells, uptake of 99mTc-tetrofosmin into SK-BR-3 cells was significantly higher, whereas uptake into MCF-7 cells was similar. CONCLUSION: In vitro data suggest that 99mTc-MIBI may be a better tracer than 99mTc-tetrofosmin for discrimination between malignant and nonmalignant breast disease. (+info)
Efficacy of morphine sulfate-augmented hepatobiliary imaging in acute cholecystitis.
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OBJECTIVE: A review of the English language literature was performed to determine the sensitivity and specificity of morphine sulfate-augmented hepatobiliary imaging for acute cholecystitis. Twenty publications, involving 914 patients, were reviewed from journals published between 1984 and 1999. The analysis of these patients has resulted in the largest combined review study to date. The sensitivity and specificity of morphine-augmented hepatobiliary imaging were calculated to be 96.1% and 88.6%, respectively. After reading this paper, the nuclear medicine technologist should be able to: (a) discuss the clinical use of morphine augmentation during hepatobiliary imaging; and (b) state the sensitivity and specificity of morphine sulfate-augmented hepatobiliary imaging. (+info)