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Biomedical subjects

G Bormans

Publications and source records attributed to G Bormans.

44 records · Page 3Linked to original sources

Metabolism of nitrogen-13 labelled ammonia in different conditions in dogs, human volunteers and transplant patients.

To investigate the rate of metabolism of nitrogen-13 labelled ammonia (13NH3) in different conditions, we have determined the relative amount of unchanged 13NH3 in the blood of dogs, volunteers and transplant patients at different times following injection. In dogs, the determinations were made under basal conditions, during adenosine administration and after coronary occlusion. The results show that adenosine administration increases the metabolic rate whereas coronary occlusion does not affect 13NH3 metabolism. For both human volunteers and transplant patients the metabolic rate of 13NH3 was assessed under basal conditions and during adenosine administration. 13NH3 metabolism proceeds faster in transplant patients than in volunteers under both conditions. Adenosine administration causes a faster 13NH3 turnover in volunteers but not in transplant patients. Application of individual metabolite correction resulted in a 16% decrease in the calculated blood flow compared to uncorrected values. A smaller difference (5%) was observed between correction with mean metabolite values and individually acquired metabolite values.

Adenosine↗

Investigation of the labelling characteristics of 99mTc-mercaptoacetyltriglycine.

S-Benzyl-, S-benzamidomethyl- and S-benzoylmercaptoacetyltriglycine were synthesized and compared in exchange labelling experiments for the preparation of 99mTc-MAG3. The rate of exchange from 99mTc-tartrate to 99mTc-MAG3 starting from the respective precursors was determined in different conditions. Labelling proceeded most rapidly starting from the S-benzoyl protected precursor but efficient labelling was also accomplished using the more stable S-benzamidomethyl- and S-benzylmercaptoacetyltriglycine. 99mTc-MAG3 was also prepared by direct labelling of unprotected mercaptoacetyltriglycine at alkaline pH. Radiochemical purity in these conditions is mainly dependent on the pH during labelling.

Animals↗

Contribution of PET in the diagnosis of recurrent colorectal cancer: comparison with conventional imaging.

The clinical value of total body PET with FDG was evaluated in 76 patients presenting with or suspected of recurrent local or distant colorectal cancer. PET results were compared to those of routine imaging (CT pelvis, CT/US liver and CXR). The accuracy of PET for local disease was 95% which was superior to CT-pelvis (accuracy 65%). PET accuracy for liver metastases (98%) compared favourably to CT/US-liver accuracy (93%). Unexpected extra-hepatic mestastases were detected by PET in 14 locations in 10 patients. Also, a primary breast cancer was found in one patient. The main value of PET appeared an improved staging of apparently resectable, local or distant recurrent disease. Thereby, a more adequate indication of major secondary surgery could be attained.

Colorectal Neoplasms↗

Histological alterations in chronically hypoperfused myocardium. Correlation with PET findings.

BACKGROUND: In patients with chronic coronary artery disease (CAD) and left ventricular dysfunction, flow/metabolic studies of the myocardium with positron emission tomography (PET) are able to distinguish viable but dysfunctional myocardium from irreversible ischemic injury and scar tissue. In this study, PET findings of blood flow and metabolism in chronically hypoperfused myocardium were correlated with histology. METHODS AND RESULTS: We studied 33 patients suffering from CAD. In each patient, myocardial blood flow and metabolism were measured with PET 1 or 2 days before revascularization. During surgery, transmural biopsies were taken from the left ventricular anterior wall and planimetrically scored for the degree of myolysis (sarcomere loss). The amount of connective tissue was calculated using morphometric techniques. Contrast ventriculography demonstrated abnormal wall motion in 23 patients. Fourteen patients with a mismatch pattern (decreased flow with preserved metabolism) in the biopsy region after quantitative analysis of the PET data showed 11 +/- 6 vol% fibrosis and 25 +/- 13% cells with sarcomere loss. The space formerly occupied by sarcomeres was mainly replaced by glycogen and mitochondria. A significant wall motion improvement was noted 3 months after surgery. Nine patients showed a match pattern (concordant flow/metabolism defects). The biopsies revealed 35 +/- 25% fibrosis and 24 +/- 15% glycogen-storing cells. The biopsies of the 10 patients with normal anterior wall motion showed 8 +/- 4% fibrosis and 12 +/- 8% glycogen-accumulating cells. CONCLUSIONS: It can be concluded that areas with impaired wall motion and a PET match pattern show extensive fibrosis. Regions with reduced flow and preserved FDG metabolism, however, contain predominantly viable cells. In these regions, significant recovery of wall motion is found after revascularization. Regions with normal wall motion contain predominantly viable cells. Cells with reduced contractile material and increased glycogen content are mainly found in areas with wall motion impairment but are also present in areas with normal wall motion and a severe stenosis of the coronary vessel.

Biopsy↗

Different perceptual tasks performed with the same visual stimulus attribute activate different regions of the human brain: a positron emission tomography study.

To investigate the processing of visual form in human cerebral cortex, we used the PET (positron emission tomography) activation technique to compare the human brain regions that are involved in a visual detection task and two orientation discrimination tasks: the temporal same-different (TSD) task, which includes a short-term memory component, and the identification (ID) task, which is without this component. As a control task we used passive viewing. Stimuli were identical in all four tasks. Subtraction of passive viewing from detection showed that the detection task activates early visual cortical regions (areas 17/18) as well as several motor brain regions, while decreasing activity in several higher order frontal, temporal, and parietal regions. Comparing the ID task to the detection task revealed no further visual cortical activation, while comparison of the TSD task to the detection task revealed an activation of several right visual cortical regions, one of which remained significant after the subtraction of ID from TSD (right area 19). These experiments demonstrate the task dependence of visual processing, even for very closely related tasks, and the localization of the temporal comparison component involved in orientation discrimination in human area 19.

Adult↗

Evaluation of 99mTc-mercaptoacetyltripeptides in mice and a baboon.

Different derivatives of MAG, carrying amino acids such as D- or L-alanine, D-serine, D-2-aminobutyric acid, D-valine or D-phenylglycine were synthesized and their 99mTc-complexes were evaluated in mice and a baboon. The efficiency of renal handling of the examined 99mTc-complexes is influenced not only by their lipophilicity but also to a great extent by their configuration and the site of substitution. The renal excretion characteristics of 99mTc-MAGAG-DA are superior to those of 99mTc-MAG3 and the studied 99mTc-complexes in both animal species. In an attempt to improve the renal handling of 99mTc-MAG3 and to evaluate the effect of derivatization we have synthesized different derivatives of MAG3 in which one or more glycyl groups are replaced by other amino acids such as D- or L-alanine, D-serine, D-2-aminobutyric acid, D-valine or D-phenylglycine. Due to the presence of a chiral centre in the ligand core, exchange labelling of each of the MAG3 derivatives results in the formation of two diastereomeric technetium complexes. These isomers were separated by HPLC and evaluated in mice. Biodistribution in mice indicates that the efficiency of renal handling of the examined 99mTc-complexes is not only influenced by their lipophilicity but also to a great extent by their configuration. The renal excretion characteristics of isomer DA of 99mTc-MAGAG in mice are superior to those of all other studied 99mTc-complexes and also of the reference compound [131I]Hippuran. The isomers LB of several alanyl derivatives of 99mTc-MAG3 exhibit a pronounced renal retention in both mice and baboon. The results of the evaluation in a baboon confirm the superiority of 99mTc-MAGAG-DA over 99mTc-MAG3 and the other studied 99mTc-complexes.

Amino Acid Sequence↗

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↗