Biomedical subjects

D Blok

Publications and source records attributed to D Blok.

17 recordsLinked to original sources

PubMed2004

Feasibility study on the retention of superporous hydrogel composite polymer in the intestinal tract of man using scintigraphy.

In recent years, many complex oral drug delivery systems have been developed using various polymers in order to achieve better drug targeting and drug absorption in the intestinal tract. Superporous hydrogel (SPH) and SPH composite (SPHC)-based drug delivery systems were also developed for the targeted delivery of peptide drugs into the intestinal tract. In the present study, the retention time of SPHC polymer is studied in man using the scintigraphy technique. To that purpose, SPHC polymers were radiolabelled with Tc-99m and administered orally in an enteric-coated gelatin capsule. The location of the radiolabelled polymer was monitored in five healthy volunteers while the subjects were sitting in front of a large field of view gamma camera. The results showed that enteric-coated gelatin capsules remained in the stomach for 75 to 150 min after oral administration to fasted volunteers and that the SPHC polymers thereafter attached to the upper part of the small intestine for at least 45 to 60 min due to their mechanical fixation properties. No discomfort was observed in any of the volunteers after oral administration of these polymers, which indicates that they are safe to be applied for oral drug delivery systems in man.

Administration, Oral↗

PubMed2001

99mTc-labeling experiments on CCK(4) by a direct method.

99mTc-labeling studies have been performed on CCK(4) fragment of cholecystokinin, starting from 99mTc-pertechnetate, by using tin(II)pyrophosphate or tin(II)gluconate as reducing agents, together with NaBH(4) acting as a stabilizing agent of tin(II). Gluconate has been used as exchange ligand in the carrier added experiments and in the syntheses of 99Tc-CCK(4) and Re-CCK(4) complexes to be able to reproduce at macroscopic level the same chemical reactions occurring at non carrier added conditions. 99mTc-labeling yields higher than 95% have been achieved depending on Sn(II) concentration, CCK(4)/gluconate ratio, reaction time and applied temperature. The species produced with 99mTc, 99Tc, and cold rhenium nuclides have been compared by means of HPLC measurements, which showed similar retention times and thus probably the same species in the three situations.

Borohydrides↗

PubMed1999

Peptide radiopharmaceuticals in nuclear medicine.

This article reviews the labelling of peptides that are recognised to be of interest for nuclear medicine or are the subject of ongoing nuclear medicine research. Applications and approaches to the labelling of peptide radiopharmaceuticals are discussed, and drawbacks in their development considered.

Animals↗

PubMed1999

Experiments on a new phosphine-peptide chelator for labelling of peptides with Tc-99m.

A phosphine-containing ligand providing a N-[N-[3-(diphenylphosphino)propionyl]glycyl]-L-S-benzyl-cystein (PNNS) donor atomset for the chelation of 99mTc was studied in labelling experiments with a model peptide (tetragastrin, cholecystokinin-fragment). The peptide was conjugated to the ligand chelator by active ester chemistry either before or after radiolabelling. Both the chelator-conjugate and the preformed chelate approaches resulted in the same radiolabelled isomers of the ligand peptide. Sequence and reaction conditions influence yield and purity.

Chelating Agents↗

PubMed1996

New peptide and protein drugs.

A view is presented on a number of recent developments, the present state and the perspectives, especially from a pharmacotherapeutic viewpoint, for peptide and protein drugs. The expanding use and the increasing experience create new pharmacotherapeutic modalities. Peptide and protein drugs comprise among others proteins isolated from human sources, and peptides and proteins made by biotechnology including monoclonal antibodies, recombinant human hormones, cytokines and growth factors. In the field of vaccine development also innovation is taking place. Optimal application schemes of these drugs may not have been reached and (clinical) pharmacists should contribute to the optimization. Since recombinant technology has abolished scarcity for a number of these drugs--especially 'physiological' substances--special ethical problems regarding an unlimited application or expansion of the indications may arise.

Antibodies, Monoclonal↗

PubMed1995

A new 99mTc labelling method for leucocytes: in vitro and in vivo comparison with 99mTc-HMPAO.

A new method for the labelling of mixed leucocytes with 99mTc-tropolone was optimized and compared with a 99mTc-HMPAO leucocyte labelling procedure in vitro and in vivo. In the present study, leucocytes obtained from patients suffering from Crohn's disease, were isolated and labelled with 99mTc-HMPAO or labelled according the new 99mTc-tropolone procedure using 9.8 mM tropolone, 1 microM stannous chloride and 0.8 mM potassium borohydride (KBH4) at pH 5.5-6. Labelling efficiency with 99mTc-tropolone yielded 92 +/- 3%, which is higher compared to the 99mTc-HMPAO labelling procedure (64 +/- 13%) using 10(8) of leucocytes. In vitro stability and viability of both the tropolone and the HMPAO labelled cells was investigated. The viability test of the 99mTc-labelled leucocytes was performed in autologous plasma at 37 degrees C and compared with unlabelled leucocytes. After 18 hours of incubation a significant (P < 0.05) higher stability was observed for 99mTc-tropolone labelled leucocytes (84 +/- 5%) compared with that of 99mTc-HMPAO labelled leucocytes (73 +/- 5%). The viability of the 99mTc-labelled leucocytes observed for both labelling procedures was similar to unlabelled leucocytes. In vivo experiments were performed in mice. 99mTc-tropolone or 99mTc-HMPAO labelled murine mixed leucocytes were injected in mice, with a Staphylococcus aureus ATCC 25923 thigh infection. Analysis of scintigraphic images yielded a faster clearance of the 99mTc-tropolone labelled leucocytes. This was most likely due to a significant (P < 0.02) higher liver uptake at 4 hours after administration of the 99mTc-tropolone labelled leucocytes (19%) in comparison with 99mTc-HMPAO labelled cells (9%). Faster and significant (P < 0.02) higher accumulation of the 99mTc-tropolone labelled leucocytes was observed at the site of infection compared with 99mTc-HMPAO labelled leucocytes at all time-intervals after the administration of the 99mTc-labelled leucocytes. The new 99mTc-tropolone leucocyte labelling procedure, offers an attractive low-cost agent for research purposes.

Abscess↗

PubMed1993

Prospective comparative study of technetium-99m-WBCs and indium-111-granulocytes for the examination of patients with inflammatory bowel disease.

In a prospective comparative study of 14 patients with inflammatory bowel disease (IBD), the abilities of 99mTc-HMPAO labeled white blood cells (WBCs) and 111In-granulocytes to assess the presence and location of active disease were compared. The two examinations were carried out within 2 wk of each other. Scintigraphically concordant positive or discordant segments were evaluated by radiologic or endoscopic examination performed within 14 days. When bowel segments were compared, concordance was found for 102/111 (91.8%) segments between 99mTc-WBC images obtained at 1 hr after injection and 3-hr 111In-granulocyte images. For five of five 99mTc-WBCs positive/111In-granulocyte negative segments, it could be proven that the 99mTc-WBC result was caused by active disease. For patients, 99mTc-WBC scintigraphy detected four more patients with active disease than 111In-granulocytes (11 and 7 patients, respectively). Technetium-WBCs was superior in the assessment of active disease, especially for small bowel segments. We conclude that early imaging 1 hr after the injection of 99mTc-WBCs can reliably replace 111In-granulocyte scintigraphy in IBD patients because the radiopharmaceutical is available on a daily basis. Thus, there is less radiation burden to the patient and cell separation is simpler and less time-consuming.

Adult↗

PubMed1992

A prospective comparison of 99mTc-labeled polyclonal human immunoglobulin and 111In granulocytes for localization of inflammatory bowel disease.

There is a need for an easily prepared radiopharmaceutical agent for the detection of inflammation and infection. In a group of 14 patients with inflammatory bowel disease (IBD), the detection of actively involved intestinal segments by nonspecific human polyclonal immunoglobulin (IgG) labeled with 99mTc was compared with that of 111In granulocytes. To determine the specificity of 99mTc-IgG scintigraphy, 8 control patients without clinical indications of intestinal inflammation were examined. 99mTc-IgG was found in the left colon in 8 and in the right colon in 7 of the 8 controls 4 hours after the injection. At that time of scintigraphy only 4 IBD patients exhibited a more intense accumulation at the site of the intestinal segments with active disease. In contrast, in a randomized comparison with 111In granulocytes scintigraphy was positive in 11 patients with the latter technique. Moreover, fewer diseased segments were seen in the 4 patients with positive 99mTc-IgG scintigraphy (6 versus 12 with 111In granulocytes). In view of the low sensitivity and specificity, it is concluded that 99mTc-IgG is not suitable for the scintigraphic staging of IBD patients.

Adolescent↗

PubMed1991

Elimination of soluble 123I-labeled aggregates of IgG in patients with systemic lupus erythematosus. Effect of serum IgG and numbers of erythrocyte complement receptor type 1.

Using soluble 123I-labeled aggregates of human IgG (123I-AHIgG) as a probe, we examined the function of the mononuclear phagocyte system in 22 patients with systemic lupus erythematosus (SLE) and 12 healthy controls. In SLE patients, a decreased number of erythrocyte complement receptor type 1 was associated with less binding of 123I-AHIgG to erythrocytes and a faster initial rate of elimination of 123I-AHIgG (mean +/- SEM half-maximal clearance time 5.23 +/- 0.2 minutes, versus 6.58 +/- 0.2 minutes in the controls), with possible spillover of the material outside the mononuclear phagocyte system of the liver and spleen. However, multiple regression analysis showed that serum concentrations of IgG were the most important factor predicting the rate of 123I-AHIgG elimination. IgG concentration may thus reflect immune complex clearance, which in turn, would influence the inflammatory reaction, in SLE.

Adolescent↗

PubMed1990

Detection of inflammatory lesions with radiolabelled immunoglobulins.

Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials of Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection were injected with Tc 99m-immunoglobulin, Tc 99m-albumin or gallium citrate Ga 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with gallium.

Animals↗

PubMed1990

Comparison of four commercially available 81Rb-81mKr generators: quality testing using a breathing lung phantom.

Four commercially available 81Rb-81mKr generators, including their elution systems, were compared. Considerable differences in useful output between the various generators were found. When a standardized elution system was used, the differences became much less. Differences in the tubing and inaccuracy of the flow meters were found to be the major causes of the original differences. The user should be aware of a loss of output that may occur when the generator is eluted with dry air.

Humans↗

PubMed1989

Image quality and radiopharmaceutical parameters of indium-111 granulocytes in scintigraphy of inflammatory bowel disease.

This study was undertaken to investigate the influence of various parameters of injected autologous 111In labelled granulocytes on scintigraphic image quality. Forty-two scintigrams of 37 patients with inflammatory bowel disease were evaluated. The images were divided into three groups according to quality: good, intermediate and poor. The relationships between image quality and such radiopharmaceutical parameters as injected dose of 111In, number of injected cells and specific activity were investigated. It appeared that in order to obtain interpretable images, a specific activity of at least 85 kBq 111In/million cells was necessary. The activity of the injected dose must exceed 7 MBq if poor quality images and very long acquisition times are to be avoided.

Cycloheptanes↗

PubMed1989

A new method for protein labeling with 99mTc.

A method is described for labeling proteins with 99mTc, the radionuclide of choice in diagnostic nuclear medicine. Labeling efficiency, stability of label attachment and retained biological behaviour, e.g. immunoreactivity of monoclonal antibodies after radiolabeling are demonstrated. An application of a 99mTc-labeled anti-fibrin monoclonal antibody in radioimmunoimaging of thrombi is presented.

Albumins↗

PubMed1989

Are activity indices helpful in assessing active intestinal inflammation in Crohn's disease?

We have investigated the correlation of 24 h and 48 h faecal Indium-111 excretion with each other and with several clinical activity indices for Crohn's disease (CD): Crohn's disease activity index (CDAI), activity index (AI), simple index (SI), Oxford score, and laboratory parameters, such as ESR, serum albumin, orosomucoid, C-reactive protein, alpha-l-antitrypsin (alpha 1-AT) faecal concentration, and alpha 1-AT clearance in 58 CD patients (37 with small bowel and 21 with colonic disease). A significant correlation was found between 24 and 48 h faecal Indium-111 excretion for small bowel (r = 0.708, p less than 0.0001) and colonic disease (r = 0.994, p less than 0.0001). The median faecal Indium-111 excretion for colonic involvement (4%; 0.15-50% median and range) was significantly (p less than 0.005) higher than that for small bowel disease (0.45%; 0.03-2.9%). No significant correlation was found between faecal Indium-111 excretion and any activity index in the patients with small bowel disease, while in the group of patients with colonic localisation only the AI showed a significant correlation (r = 0.593, p less than 0.02). Faecal Indium-111 excretion was significantly correlated with alpha 1-AT clearance (r = 0.712, p less than 0.0001) and faecal alpha 1-AT concentration (r = 0.750, p less than 0.0001) in small bowel and in colonic localisation (r = 0.530, p less than 0.02 and r = 0.444, p less than 0.05). Serum albumin was significantly correlated only in the group of patients with colonic disease (r = -0.593, p less than 0.05). The present study shows poor agreement between activity indices, serum parameters of activity and faecal Indium-111 excretion. As a good correlation was found with the alpha1-clearance, which reflects losses into the gut, these results may suggest that faecal Indium excretion does not only reflect activity of inflammation, but my relate to the extent of intestinal ulceration.

Adolescent↗

PubMed1988

Is radiolabelled sucralphate scintigraphy of any use in the diagnosis of inflammatory bowel disease?

Previous optimistic reports led us to undertake a study to determine the value of 99Tcm-sucralphate scintigraphy in the assessment of localization and extent of active inflammatory bowel disease. Eight patients were studied; four had Crohn's disease (three small bowel and one colon localization) and four patients had ulcerative colitis. The results obtained by scintigraphy were compared with those obtained by diagnostic radiology and/or endoscopy. In five patients indium-111 granulocyte scintigraphy was also performed. 99Tcm-sucralphate scans showed total discrepancy with standard investigations in four patients and partial discrepancy in the other four. Furthermore, it was difficult from the images to decide whether the radiolabelled sucralphate indicated true inflammation or normal distribution of the radiopharmaceutical. Patient acceptability was very low due to frequent scanning times and the recommended purgation which was not well tolerated and is contraindicated in severely ill patients. We conclude that this technique is not a good screening test for diagnosing inflammatory bowel disease and we have, therefore, discontinued the study.

Adult↗

PubMed1987

A new method for 99Tcm-labelling of proteins with an application to clot detection with an antifibrin monoclonal antibody.

A new method is described for labelling proteins with 99Tcm. Labelling of fibrinogen resulted in a radiochemical yield of about 80%. After clotting this 99Tcm-labelled fibrinogen with trombin, an equal percentage of the radioactivity was found in the clot illustrating the retained biological behaviour of this labile protein after our labelling procedure. Labelling of a monoclonal antibody (MoAb) directed against fibrin resulted in a labelling percentage of about 70%. Immunoreactivity of this antifibrin (Y22) is hardly affected by the procedure as demonstrated by a double-sandwich enzyme immunoassay (EIA). Perfusion experiments on a gamma camera in which a plasma clot in a glass chamber was perfused with plasma containing 99Tcm-labelled Y22 revealed an excellent uptake of activity by the clot within 2 h. Finally an animal experiment is presented which showed clear visualization of the thrombi in the jugular vein and the abdomen of a rabbit by scintigraphy after the administration of 99Tcm-labelled antifibrin (Y22).

Animals↗

PubMedDate not supplied

Technetium-99m nanocolloid for the scintigraphic assessment of inflammatory bowel disease in the colon: its value in comparison with indium-111-labelled granulocytes.

The usefulness of 99mTc-nanocolloid for the assessment of localization and disease activity of colitis in patients suffering from inflammatory bowel disease (IBD) was investigated in 10 patients. Results of 99mTc-nanocolloid scintigraphy were compared with Indium-111 autologous granulocyte scintigraphy and the activity index according to Van Hees. In none of the patients a true positive result of the 99mTc-nanocolloid scintigraphy was encountered, while 111In-granulocyte scintigraphy was positive in 7 of 10 patients with active disease. Radioactivity became visible in the small bowel starting 2 h after injection of 99mTc-nanocolloid most likely because of excretion by the liver of degradation products of the radiopharmaceutical. The authors conclude that despite a previous communication 99mTc-nanocolloid cannot replace 111In-granulocytes for the assessment of IBD patients with active colitis.

Adult↗