The use of 111In-labelled autologous neutrophils in imaging myocardial infarction.
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Biomedical subjects
Publications and source records attributed to A M Millar.
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The uptake of indium-111 labelled neutrophils was examined in 30 patients with acute myocardial infarction by planar imaging and single photon emission computed tomography. The time from venepuncture to reinjection of the autologous labelled neutrophils was less than 2.5 hours and imaging was carried out 24 hours later. Twenty three patients had a positive uptake of neutrophils in the myocardium and imaging was improved by single photon emission computed tomography. There was a significant difference between the intervals from the onset of chest pain to injection of labelled neutrophils between patients with positive and negative images; early reinjection was more likely to produce a positive image. Indeed, all nine patients reinjected within 18 hours of the onset of symptoms had positive images. The results suggest that the stimulus for activation and migration of neutrophils is transient; this is an important factor if neutrophil release products play a role in cell damage after coronary occlusion.
using a single step separation procedure, we have developed a method for labelling human neutrophils with 111In-oxine. This method allows a rapid separation of neutrophils from whole blood, with negligible mononuclear or red cell contamination. Preliminary studies using 111In-labelled neutrophils show minimal lung retention and early accumulation in the spleen consistent with viable cells. In addition, focal accumulation of 111In has been imaged in patients with localized inflammation or sepsis.
We have compared the cost of providing routine lung ventilation scintigraphy using 127Xe with other radioactive gases in 100 patients. The physical properties of 127Xe permit a logical imaging sequence where a ventilation study is only carried out if indicated by perfusion scintigraphy which is performed first. With 133Xe, all patients must be ventilated prospectively, or a preselection carried out based on radiographic appearances at the time of imaging. This results in a greater number of ventilation studies than with 127Xe. Despite the greater cost per study of 127Xe, the overall cost of providing a routine diagnostic service with this gas is no more than that of using 133Xe in selected patients. The cost of ventilating all patients prospectively with 133Xe is considerably greater than using 127Xe only when indicated by abnormal perfusion images. If ventilation imaging is to be available at all times, either isotope of xenon costs very much less than 81Krm. We conclude that 127Xe is the radiopharmaceutical of choice for routine lung ventilation scintigraphy.
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It is common practice to dispense radiopharmaceuticals into empty sterile vials for dispatch to the departments where they are to be administered. It has been noted that on withdrawal of technetium-99m dimercaptosuccinic acid injections (99Tcm-DMSA) which have been dispensed into such vials, the activities obtained are lower than expected. To explain this phenomenon, the adsorption of 99Tcm-DMSA onto commercially available, empty, sterile vials has been investigated. The 99Tcm-DMSA solutions were prepared using kits from two manufacturers and were tested in vials from two manufacturers and the original kit vials. Adsorption of 99Tcm in one DMSA/vial combination after storage for 4 h was 49.6% (+/- 4.5% S.E.M.), but typically, adsorption was approximately 12% after 4 h. Although rate of adsorption was found to vary with storage conditions, no conditions satisfactorily overcame the effect. In vials from one manufacturer, the 99Tcm adsorption was predominantly on the glass, while in vials from the other, it was predominantly on the rubber stopper. It is concluded that the compatibility between vials and radiopharmaceuticals must be investigated in the hospital radiopharmacy.
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The effect of different methods of stannous pyrophosphate (SnPYP) administration on a modified in vivo technique for labelling red blood cells (RBCs) with 99mTc has been studied. Retention of 99mTc in the bloodstream was measured and parallel in vitro RBC labelling experiments were performed. After administration of SnPYP or a mixture of SnPYP and heparin via the metal needles of intravenous cannulae, the mean 30-min retentions of 99mTc were 96.8% (SD 8.6) and 95.3% (SD 12.4) respectively and the mean in vitro labelling efficiencies were 86.9% (SD 5.0) and 81.9% (SD 18.2) respectively. When the SnPYP was administered via teflon cannulae, the mean 30-min retention of 99mTc was 40.0% (SD 16.7) and the in vitro labelling efficiency was 18.7% (SD 27.0). Reduced RBC labelling and rapid clearance of 99mTc from the bloodstream were not explained by adsorption of stannous ion or pyrophosphate onto the teflon cannulae or retention of SnPYP in the cannulae. When labelling RBCs with 99mTc it is important that SnPYP is not injected via a teflon cannula.
Using an experimental model of acute pancreatitis in the rat, we have studied changes in the biophysical properties of lungs and intrapulmonary fibrin deposition in this condition. Acute pancreatitis is associated with a significant decrease in pulmonary compliance (p less than 0.01) and a significant increase in lung weight (p less than 0.01) compared with a control sham operation group. These changes are associated with a 24% increase in intrapulmonary 125I fibrinogen deposition (p less than 0.01), and an 18% increase in 125I fibrinogen deposition per gram of lung tissue (p less than 0.05) in acute pancreatitis, compared with a control sham operation group. The increased fibrinogen deposition is abolished by treatment with low dose heparin. Using the same animal model changes in pulmonary ultrastructure are shown using scanning electron microscopy. The results indicate that pulmonary abnormalities are associated with intrapulmonary fibrin deposition in experimental acute pancreatitis and these findings may be relevant to the well described respiratory complications of the condition in man.
The etiology and pathogenesis of acute necrotizing hemorrhagic pancreatitis remain controversial. Recent work has suggested that an early fall in pancreatic blood flow, causing ischemia, may be the initiating factor. Using an established rat model of hemorrhagic pancreatitis and the fractional indicator distribution technique with 86RbCl, pancreatic blood flow and tissue perfusion have been measured at various times in the condition. Six groups of ten rats were studied: control sham operation and pancreatitis groups were sacrificed at 1, 6, and 24 hr. Pancreatic blood flow (% of cardiac output) and perfusion (blood flow/g tissue) were measured. Blood flow was increased by a maximum of 53% at 1 hr (P less than 0.001) and remained elevated for 24 hr, and perfusion was increased by a maximum of 70% (P less than 0.001) at 1 hr and remained elevated at 6 hr. Pancreatic perfusion declines after 6 hr due to increasing gland edema. The results demonstrate a significant increase in pancreatic blood flow and perfusion in experimentally induced acute pancreatitis, suggesting a primary inflammatory response, and refute the ischemic etiological theory.
2 micron microspheres of albumin were prepared and labelled with 99mTc according to published methods. However, when the labelling technique was repeated without the inclusion of microspheres, apparent labelling, which was attributed to the formation of a 99mTc tin colloid, was still observed. It was not possible to identify 99mTc tin colloid in the presence of 99mTc microspheres. To establish conditions under which there was no 99mTc tin colloid formation, labelling, with and without microspheres, was studied at low pH for a range of SnCl2 X 2H2O concentrations. A "kit" containing 0.4 mg of microspheres and 1 microgram of SnCl2 X 2H2O in 1 ml of 25 mM HCl gave optimum labelling of 88.3% (SD 3.9, n = 38). Unlabelled and labelled kits were stable for 1 and 3 h respectively. Before administration, the microspheres were resuspended in ethanol, in which they were stable for 6 h. None of the preparations contained 99mTc tin colloid.
A method for the separation of the radiopharmaceutical iodohippuric acid ([123I]IHA) from the two impurities produced in the labelling reaction, iodide (123I-) and iodobenzoic acid ([123I]IBA) has been developed using reversed-phase high performance liquid chromatography (h.p.l.c.). The effect of eluent pH on the separation of the three compounds was studied. An eluent consisting of methanol: 0.1 M acetic acid (30:70) adjusted to pH 4.0 with NaOH gave optimum phase capacity ratios of -0.21 for I-, 0.93 for IHA and 1.54 for IBA. On the chromatograph used, this corresponded to an analysis time of 4 min per sample. To recover 123I- from the column with a good peak shape, it was found necessary to include sodium iodide (1 mg/100 ml) in the eluent. The recoveries of 123I-123IHA and 123IBA from the column were found to be 100.6% (s.d. 1.3), 100.2% (s.d. 2.1) and 98.1% (s.d. 1.2) respectively (n = 10 for each compound). H.p.l.c. was compared with the standard thin layer chromatographic (t.l.c.) method of analysis on 10 preparations of [123I]IHA which gave a mean radiochemical purity of 99.1% (+/- 0.2 s.e.) by h.p.l.c. and 98.3% (+/- 0.2 s.e.) by t.l.c. This difference was found to be significant (P less than 0.05) and an explanation for this difference is proposed. A coefficient of variation of 0.1% on the results from the repeated analysis (n = 20) of one preparation of [123I]IHA, demonstrated that the h.p.l.c. method was capable of very high precision.
Radioactive microspheres could offer several advantages over gases in the investigation of pulmonary ventilation. Monodisperse microspheres of human serum albumin have been produced using a spinning-disc generator, and kits were prepared for subsequent labelling with technetium-99m. The average labeling efficiency was 88% and unlabeled Tc-99m was removed before aerosol delivery. A simple system was constructed to nebulize and deliver dry monodisperse microspheres. The ventilation images obtained were compared quantitatively with the corresponding krypton-81m images, subdividing the lung regions into inner, central, and peripheral zones. No significant difference was found in the proportions of the total counts for any lung region. There was good agreement between the distributions of microspheres obtained on separate days (r = 0.97, p less than 0.0001), An "aerosol penetration index" was defined as the ratio of the peripheral to the inner counts for the microspheres normalized by the corresponding ratio for krypton-81m. The mean value of this index for 16 normal subjects was 0.98 +/- 0.23 (s.d.), indicating that the microspheres had achieved penetration of the lung periphery. For patients with chronic obstructive lung disease, more localized defects were observed with the microspheres than with krypton-81m. The mean penetration index for this group was only 0.69 +/- 0.21 (s.d.). This was significantly different from the value for normal subjects (p less than 0.002).
We have investigated the suitability of five different commercially available kits which provide human serum albumin (HSA) labelled with technetium 99m (99mTc) for cardiac blood pool imaging. Four of these products were one-step processes using stannous chloride as the reducing agent; the fifth was based on an electrolytic reduction. In addition, we also assessed our own modification of the electrolytic method. We measured the radiochemical purity by precipitation with trichloroacetic acid and by gel filtration on a Biogel P4 column. In addition, we measured the clearance of radioactivity from the blood at frequent time intervals after intravenous injection. Each product was assessed in separate groups of six patients. The labelling efficiency of the one-step kits varied between 73 and 93% compared with 94 and 98% for the electrolytically labelled albumin. The blood clearance for all one-step kits was significantly faster than that obtained for the radiopharmaceuticals prepared by the electrolytic method. We conclude that HSA labelled with 99mTc by the electrolytic method is to be preferred.