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Biomedical subjects

M De Roo

Publications and source records attributed to M De Roo.

At least 55 records · Page 3Linked to original sources

Synthesis and biological characteristics of the four stereoisomers of 99mTc-N,N'-bis-(mercaptoacetyl)-2,3-diaminopropanoate.

To study the differences in biological behaviour between the four stereoisomers of 99mTc-CO2-DADS we synthesized both the L- and D-isomer of N,N'-bis-(benzoylmercaptoacetyl)-2,3-diaminopropanoic acid ethyl ester. The N2S2 ligands were labelled with 99mTc by the dithionite reduction method in alkaline medium to hydrolyze the ester function. Each isomer yielded two diastereomeric 99mTc-complexes, that were separated by RP-HPLC to finally obtain the four isomers of 99mTc-CO2-DADS. The biodistribution of the isomers was determined in mice and a baboon. The study in mice indicates that only the LB-isomer is responsible for the high liver uptake reported for (DL)-99mTc-CO2-DADS-B (Fritzberg et al. J. Nucl. Med. 23, 592-598, 1982). The rate of renal extraction and hepatobiliary excretion of the three other isomers is comparable to that of [131I]o-I-hippurate. Baboon renograms for the LA- and DA-isomers are similar to that of [123I]o-I-hippurate. The renogram of the DB-isomer resembles more the 99mTc-DTPA renogram, whereas the LB-isomer exhibits a 99mTc-DMSA-like renal build-up. It appears that minor configurational changes can drastically alter the renal handling of these bisamide bisthiol 99mTc-tracer agents.

Alanine↗

Evaluation of the effect of thrombolytic treatment on infarct size and left ventricular function by enzymatic, scintigraphic, and angiographic methods. The European Cooperative Study Group for Recombinant Tissue Type Plasminogen Activator.

In a double-blind trial of the European Cooperative Study Group, 721 patients with acute myocardial infarction of less than 5 hours' duration were given either 100 mg recombinant tissue-type plasminogen activator (rt-PA) intravenously over 3 hours or an equivalent placebo infusion. In a subset of 312 patients, infarct size was assessed by the cumulative myocardial release of alpha-hydroxybutyrate dehydrogenase (HBDH) during the first 72 hours and by planar thallium scintigraphy (index of hypoperfusion) performed 10 to 22 days after the acute event. Left ventricular ejection fraction (LVEF) was determined by contrast and nuclear angiography. The median values of HBDH during the first 72 hours were 20% lower and the median values of thallium-201 28% smaller in the rt-PA group in comparison with controls. A significant but limited improvement of angiographic LVEF (2 absolute percentage points) was also shown in the patients treated with rt-PA. A moderate but statistically significant linear association between both measurements of infarct size and LVEF was found.

Adult↗

Background correction in factor analysis of dynamic scintigraphic studies: necessity and implementation.

In factor analysis, structures are separated on the basis of their temporal behaviour, even if there is a partial overlap. Usually, the temporal behaviour of the system under study cannot be sampled in its true form due to a total overlap by the background. In the ROI (region of interest) method, background subtraction is used as a means to correct the problem. In factor analysis, this problem has been ignored for a long time. We prove that the factor analysis method gives incorrect results when there is a total overlap of a structure. By assuming a local homogeneity of the overlapping structure, we can greatly improve the solution found. Compared with the classical ROI method, our method is operator independent and organ specific.

Biophysical Phenomena↗

Visualization and characterization of gastric contractions using a radionuclide technique.

With the use of the radionuclide gastric-emptying test and a new data processing method, the contraction characteristics of the stomach were analyzed. After ingestion of a radiolabeled test meal, dynamic images of the stomach were acquired and analyzed to determine the frequency, amplitude, and rate of gastric contractions in healthy subjects. The frequency of antral contractions was found to be inversely related with food retention in the stomach; in contrast, the amplitude of the contractions decreased progressively during the course of gastric emptying. The peaks of both antral contraction and filling rate and the time of their occurrence remained constant throughout gastric emptying. The observed patterns of phase distribution and sequential phase changes of the food in the stomach confirmed noninvasively what was already known from invasive technique, i.e., that the proximal stomach does not undergo phasic contractions and that, in the distal stomach, smooth muscle contraction originates in midcorpus and propagates aborally to the pylorus. The scintigraphic test can be used to noninvasively and quantitatively characterize gastric motor function and to delineate the spatial sequence of gastric contractions. This technique can be applied to study the pathophysiology of gastric emptying in various motor disorders.

Adult↗

Effect of proximal vagotomy and Roux-en-Y diversion on gastric emptying kinetics in asymptomatic patients.

The role of the distal stomach in gastric emptying was studied. Ten patients with proximal gastric vagotomy (PV) and 10 age-matched patients with Roux-en-Y gastro-jejunostomy (R-Y) were compared with 10 healthy controls. Gastric emptying of solids and liquids was determined by the use of Tc-99m SC scrambled eggs and In-111 DTPA. In PV, gastric emptying of both solids and liquids was delayed; the prolongation with solids was mainly accounted for by an abnormal lag phase. In R-Y patients, no lag phase was observed, and the solid emptying curve pattern was characterized by early rapid emptying followed by very slow emptying. Both the solid and liquid phases were prolonged. The lag phase is affected by proximal vagotomy and is mainly determined by the distal stomach, which appears to be essential for normal emptying.

Adult↗

Tc-99m HM-PAO labelled leucocyte scanning for detection of infection in orthopedic surgery.

The use of labelled granulocyte scintigraphy is recognized as a reliable method for detecting osteomyelitis and other skeletal sepsis. Tc-99m hexamethyl propyleneamine oxime (Tc-99m HM-PAO), a lipophilic chelate offers the advantages of availability, lower radiation dose and higher image resolution, compared to other labelling agents. We have scanned 36 orthopedic patients with suspected infection, using autologous granulocytes labelled with Tc-99m HM-PAO. In all cases, scans were compared with clinical, microbiological and/or surgical findings. Sensitivity was 94% and specificity was 80%. We therefore believe that Tc-99m HM-PAO leucocyte scanning provides a useful method for detecting osteomyelitis and other skeletal infections.

Adolescent↗

Intravenous erythromycin dramatically accelerates gastric emptying in gastroparesis diabeticorum and normals and abolishes the emptying discrimination between solids and liquids.

Erythromycin, a macrolide antibiotic, has recently been shown to have a motilin like effect on gastrointestinal muscle strips. In this study, we have evaluated the effect of erythromycin on patients with delayed gastric emptying and healthy subjects using the dual radionuclide technique. Twelve patients with gastroparesis diabeticorum and ten healthy age- and sex-matched controls were studied. Gastric emptying of solids and liquids was determined using 99mTc-SC scrambled egg and 111In-DTPA in water. Following a baseline study and on a separate day, each patient and control received a 15-min i.v. perfusion of erythromycin starting at meal ingestion. Eleven out of the 12 patients were restudied after a 3-wk oral administration. In patients and controls, i.v. erythromycin dramatically accelerated gastric emptying of both solids and liquids which were emptied at the same rate. After chronic oral administration, solid and liquid emptying remained significantly accelerated. Erythromycin appears to be a very powerful gastrokinetic drug. Derived compounds with the gastrokinetic effect and without the antibiotic activity could be useful in dyspeptic patients with delayed gastric emptying.

Diabetes Complications↗

Clinical experience with Tc-99m HM-PAO high resolution SPECT of the brain in patients with cerebrovascular accidents.

In order to evaluate the diagnostic contribution of brain SPECT imaging with 99mTc-HMPAO in cerebrovascular disease, we examined 92 stroke cases (144 lesions), 2 hematoma cases and 30 cases with transient neurologic symptoms. Abnormal tracer distribution is visible as zones of either hypoactivity or hyperactivity (border zone hyperemia or luxury perfusion). Remote vascularization changes could also be found (crossed cerebellar diaschisis or ipsilateral cortical perfusion reduction in thalamic or capsula interna lesions). Both X-ray CT and blood flow SPECT have comparable sensitivity in the exploration of cerebral infarction, with detection in, respectively, 89.5% and 87.5% of the lesions. False negative scintitomographic images are frequently recorded in small lacunar infarcts within the basal ganglia and white matter (capsula interna). Some early infarcts and asymmetry of brain perfusion in patients with transient neurologic symptoms are frequently not detected by CT. An additional advantage of blood flow SPECT is its ability to visualize remote blood flow changes and the changing pattern of vascularization of ischemic lesions and their surrounding areas including hyperemia.

Brain↗

Thrombus imaging with an I-123-labeled F(ab')2 fragment of an anti-human fibrin monoclonal antibody in a rabbit model.

The murine monoclonal antibody MA-15C5 binds to cross-linked fibrin but not to fibrinogen. Fab or F(ab')2 fragments of MA-15C5, labeled with iodine-123, were injected intravenously into nine rabbits with a nonocclusive 0.2-mL human plasma clot in the jugular vein and into eight control rabbits. Scintigrams obtained at hourly intervals after injection of the F(ab')2 fragment revealed a significantly higher accumulation of tracer in the clot region than in the contralateral region. The relative excess of tracer in the jugular vein region was significantly greater in the study animals than in the control animals throughout the study period. Blind reading of serial scans revealed no visible tracer accumulation in seven of eight control rabbits, whereas the scans of seven of nine study rabbits showed clearly visible accumulation (sensitivity = 77%, specificity = 87%). The Fab fragment of MA-15C5 had a lower affinity and bound less avidly to the blood clot in vivo. These results suggest that the F(ab')2 fragment has better imaging properties than the Fab fragment and that it may be useful for imaging blood clots in man.

Animals↗

In vitro and in vivo evaluation of granulocyte labeling with [99mTc]d,1-HM-PAO.

The functional integrity of white blood cells labeled with [99mTc]d,1-HM-PAO containing variable amounts of the ligand or of the 99mTc activity was evaluated by enzymatic tests and by measuring random migration, chemotaxis, phagocytosis, killing, and adhesion. The ultrastructure of labeled cells was studied by electron microscopy. The tracer dose and the HM-PAO concentration did not significantly affect phagocytosis and killing. The results of the other tests remained normal. A maximum labeling efficiency of 80% was reached by incubating the granulocytes for 20 min with 10-20 mCi of [99mTc]d,1-HM-PAO containing 50 micrograms of the ligand in 1 ml of saline. There was only a slow washout of 20% of activity from the labeled cells in 24 hr. The ultrastructure was not influenced by the labeling technique. Proven infection sites of 17 orthopedic patients were clearly visualized. After a short transient lung uptake, there was a clear spleen and moderate liver uptake with early bladder and late prominent colon visualization. Because of the lower cost, favorable radiation dose and more suitable tracer characteristics, this technique is a promising alternative for 111In labeling of white blood cells.

Bacterial Infections↗

Characterization of technetium-99m-L,L-ECD for brain perfusion imaging, Part 2: Biodistribution and brain imaging in humans.

The safety, biodistribution and kinetics of a new perfusion imaging agent [99mTc-L,L]-ethyl cysteinate dimer (ECD) was evaluated in normal volunteers. Technetium-99m-L,L-ECD is a neutral, lipophilic complex, which is radiochemically pure and stable. Twelve healthy adults were injected with 25-30 mCi of 99mTc-L,L-ECD and imaged periodically for up to 24 hr. Planar imaging showed rapid brain uptake with a peak concentration of 4.9% injected dose and very slow brain washout (approximately 6% per hour during the first 6 hr). Repeat or dynamic tomographic imaging of the brain using either a rotating gamma camera or a multidetector system was performed up to 6 hr postinjection. The distribution of 99mTc-L,L-ECD in the brain did not change and was similar to the pattern seen with other perfusion agents. Background facial areas and lungs cleared rapidly. Peak blood activity was below 10% injected dose at all times and 99mTc-L,L-ECD cleared rapidly through the kidneys. Vital signs, blood and urine chemistries were normal in all volunteers and no adverse reactions were noted. These results suggest that 99mTc-L,L-ECD should be useful for routine assessment of cerebral perfusion in humans.

Adult↗

Unilateral kidney irradiation and late retreatment with cis-dichlorodiammineplatinum (II): functional measurements with 99mtechnetium-dimercaptosuccinic acid.

A rat model was used to study renal function after unilateral kidney irradiations. The left kidney was irradiated with a single dose (6-14 Gy), 2 equal sized fractions (10-16 Gy total dose) or 4 equal sized fractions (12 to 21 Gy total dose). At regular time intervals after treatment, the left kidney function was assessed with the use of 99mTc-Dimercaptosuccinic acid for a period of about 1 year. It was found that renal function declined in a dose- and time-dependent manner. The threshold dose for detecting functional impairment was 8 Gy for 1 fraction, 12 Gy for 2 fraction and 15 Gy for 4 fraction irradiations, demonstrating the sensitivity of the isotope tracer test used in these experiments. Retreatment of the rats with a single i.p. dose of 5 mg/kg cis-Dichlorodiammineplatinum (II) (cis-DDP) given at about 1 year after X ray exposure revealed an important relative decrease in the function of the irradiated compared to the unirradiated kidney. Reductions in function of 11 to 70% (depending on radiation dose and schedule) compared with control values were observed at 11 weeks after drug injection. These results demonstrate that a previously irradiated kidney is more sensitive to a subsequent treatment with cis-DDP than the contralateral hypertrophied kidney in the same animal.

Animals↗

Comparison of quantification methods of 111In-labelled platelet deposition in peripheral bypass grafts.

The action of antithrombotic drugs can be evaluated by measuring the deposition of 111In-labelled platelets on peripheral bypass grafts several days after injection. This evaluation can be performed qualitatively (visual interpretation on the daily images) or quantitatively. Four different methods which calculate the ratio of platelet uptake with a reference region are compared: two methods use a gamma camera and two a detector. A blood sample or the region under the sternal angle are used as reference. The daily ratio of the counts, recorded by a gamma camera in a region of interest covering the graft, and the blood radioactivity interpolated from a platelet survival curve appears to be the most reliable method. The information of all the ratios can be combined in a single thrombogenicity index which reflects the daily rise of a linear or exponential regression versus time.

Aged↗

A new thresholding method for volume determination by SPECT.

The quantification of organ volumes from SPECT images suffers from two major problems: image segmentation and imperfect system transfer function. Image segmentation defines the borders of an organ and allows volume measurements by counting the voxels inside this contour in all slices containing parts of this organ. A review of the literature, showed that several investigators use a fixed threshold (FT) to determine the organ pixels. It is our aim to demonstrate that the threshold has to be adapted to every single case because its value is dependent upon several factors, such as size and contrast. Therefore a threshold selection algorithm, based on the gray level histogram (GLH), is evaluated. It is nearly impossible to calculate and eliminate errors induced by the complex system response function. A correction method based on linear regression is proposed. By minimizing the relative error (sigma), a linear correlation (Y = AX + B) between the true volume (Y) and the measured volume (X) is established for three fixed thresholds (30%, 40%, 50%) and for the GLH method. The methods are evaluated on a series of nineteen phantoms with a volume range between 9.8 and 202.5 ml. The relative error is minimal for the GLH method. The whole procedure is semi-automated and virtually operator independent.

Algorithms↗