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R I Feitsma

Publications and source records attributed to R I Feitsma.

At least 19 recordsLinked to original sources
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↗
PubMed1993

The labeling of proteins and LDL with 99mTc: a new direct method employing KBH4 and stannous chloride.

A new direct labeling technique for proteins with technetium-99m (99mTc) has been developed and makes use of borohydride and stannous chloride. The method is simple and reproducible and gives a high labeling efficiency and high retention of biological activity for proteins, including polyclonal immunoglobulin (Ig), antifibrin monoclonal antibody, tissue type plasminogen activator, fibrinogen and low density lipoprotein (LDL). This method can be used in kit-format and takes about 20 min preparation time at room temperature. Both in vitro and in vivo studies indicate good stability of the label. In vivo, mice and rabbit images show significant accumulation of 99mTc-Ig at an inflammation area, 99mTc-antifibrin at a thrombus site and 99mTc-LDL in atherosclerotic lesions. The method is attractive for routine research and clinical purposes.

Animals↗
PubMed1993

Tissue distribution of bacteriochlorin a labelled with 99mTc-pertechnetate in hamster Greene melanoma.

Bacteriochlorin a (BCA), a new photosensitizer for photodynamic therapy, was labelled with 99mTc-pertechnetate following a method for the irreversible coupling of 99mTc-pertechnetate to proteins. Biodistribution studies were conducted in male Syrian Golden hamsters with hamster Greene melanoma implanted s.c. on both sides of the abdomen. After i.v. administration of 99mTc-pertechnetate-labelled BCA 17 tissue and fluid samples were analysed at time intervals ranging from 1 to 24 h. Technetium-labelled BCA showed a pronounced affinity for tissues belonging to the reticuloendothelial system. Peak activities, 1 h post-injection, were distributed as follows: lung, liver, spleen, urine > small intestine, kidney, blood, heart, stomach, large intestine > thyroid, tumour, bone, skin, muscle, eye >> brain. It is concluded that the technetium-labelled photosensitizer BCA does not accumulate selectively in neoplastic tissue.

Animals↗
PubMed1993

Potential of 99mTc-LDLs labeled by two different methods for scintigraphic detection of experimental atherosclerosis in rabbits.

In this study we evaluated two different 99mTc-labeling techniques to produce 99mTc-low density lipoprotein (99mTc-LDL) suitable for the scintigraphic delineation of experimental atherosclerotic lesions. The two methods are 1) a procedure that uses stannous chloride and sodium borohydride (borohydride method) and 2) a procedure that uses sodium dithionite as a reducing agent and that has been successfully applied in previous scintigraphic atherosclerosis detection (dithionite method). 99mTc-LDL produced by either method was injected into New Zealand White rabbits with diet-induced atherosclerotic plaques and in control rabbits. Scintigraphic images were taken 10 minutes (t = 0) and 1, 4, 8, 16, and 24 hours after injection. Clearance of plasma radioactivity was also studied. Stability of the 99mTc-LDL complex in the circulation was examined by size exclusion chromatography of plasma samples. After scintigraphy, the animals were killed, and the biodistribution of radioactivity was determined. The thoracic and abdominal aortas appeared in scintigraphic images to accumulate 99mTc over their entire length with either 99mTc-LDL preparation. The sparse imaging of focal atherosclerosis was found to be due to the fact that the aortas were covered with confluent atherosclerotic lesions. Scintigraphic image analysis showed that 24 hours after injection, the accumulated radioactivity in the abdominal aorta of the atherosclerotic rabbits was 57% and 54%, respectively, of the accumulated radioactivity in the abdominal aorta at t = 0 when the borohydride versus the dithionite method was used. In the control animals this value was 25% for the dithionite method, whereas in the borohydride method the aortas could not be detected in the images at t = 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Does haemodialysis impair macrophage Fc receptor function?

Patients treated with chronic haemodialysis are at risk of infections, possibly because of impaired function of macrophage Fc receptors. Using [123I]-labelled aggregates of human IgG ([123I]-AIgG) as a probe of Fc-receptor-mediated function, we examined eight patients treated with chronic intermittent haemodialysis (HD), eight patients treated with CAPD, eight patients with preterminal renal failure who had not yet received renal replacement therapy, and eight healthy controls. In all three patient groups the first elimination half-life of [123I]-AIgG was decreased, suggesting accelerated binding of the probe. In the HD group overall clearance of [123I]-AIgG was similar to the value found in healthy controls. In the CAPD and preterminal renal failure group clearance was decreased as compared with the HD patients. Uptake of [123I]-AIgG by liver and spleen was quantitatively similar in patients and controls, but hepatic uptake of [123I]-AIgG reached its maximum earlier in the patients treated with HD. These results suggest that Fc receptor function is not impaired in patients who undergo chronic haemodialysis.

Adult↗
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↗
PubMed1989

An antifibrin monoclonal antibody useful in immunoscintigraphic detection of thrombi.

Balb/c mice were immunized with human plasmin-generated fibrinogen degradation product Y. Spleen cells were fused with P3X63-Ag8.653 myeloma cells. A clone (Y22) was found that produces monoclonal antibodies (MoAbs) with a strong reactivity with human fibrin and only a weak reactivity with fibrinogen in an enzyme immunoassay (EIA). Y22 also reacts with fibrin of rabbits, rats, sheep, and dogs. The antibodies are of the IgG1 kappa-type and appear to be directed against a conformation-dependent epitope in the D-domain of fibrin. Experiments with 99mTc-labeled Y22 in vitro show that Y22 binds rapidly to forming clots. 99mTc-Y22 also binds to preformed plasma clots in a plasma milieu, even in the presence of high concentrations of heparin. Clot localization experiments in rabbits and rats confirm the high fibrin specificity and the potential of 99mTc-Y22 for thrombus imaging in vivo.

Abdomen↗
PubMed1989

Hemoglobin radiolabeling: in vitro and in vivo comparison of iodine labeling with iodogen and a new method for technetium labeling.

Radiolabeled hemoglobin may be a useful tool in the study of the body distribution of hemoglobin solutions developed as plasma expanders with oxygen-transporting capacity. The present investigation compares the suitability of two radiolabeling techniques for hemoglobin. 125I labeling of hemoglobin with Iodogen as iodinating agent caused major changes in the chromatographic behaviour and an accelerated plasma clearance of the labeled hemoglobin in rats. A recently developed two-step procedure for 99mTc labeling gave better results. The label had only minimal influence on the chromatographic behaviour of hemoglobin. In vivo, no free label occurred in the circulation and no transfer of the label to other plasma proteins took place. The plasma clearance of 99mTc-labeled hemoglobin in rats was slowed. However, this could be explained entirely by diminishing glomerular filtration, probably by inhibition of the dissociation of the hemoglobin molecule into dimers. The plasma clearance of hemoglobin modified by intramolecular cross-linking, which prevents dissociation of the molecule into dimers and thus excretion by the kidney, was not influenced by the label. We conclude that the 99mTc labeling procedure is suitable for in vivo distribution studies of hemoglobin when it is taken into account that the urinary excretion is underestimated. For cross-linked hemoglobin, which is more promising as plasma expander, no such restriction exists.

Animals↗
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

An in vitro model for the scintigraphic detection of thrombi using a 99Tcm-labelled antifibrin monoclonal antibody.

Because of their specific targeting properties, monoclonal antibodies have found widespread use in nuclear medicine. In this paper, a method is described for the evaluation of immunoscintigraphic parameters for the detection of thrombi, using a 99Tcm-labelled antifibrin monoclonal antibody (designated as Y22). An in vitro model was developed to evaluate the effects of various environmental conditions on uptake by plasma clots of 99Tcm-Tc-Y22 in circulating plasma on a gamma camera. The clots became visible as hotspots after approximately 1 h of circulation of 99Tcm-Y22 containing citrated plasma at 37 degrees C. Circulation of 99Tcm-fibrinogen, 99Tcm-HSA or 99Tcm-control MoAb did not show visible uptake by the clots under the same conditions. At 37 degrees C, 99Tcm-Y22 accumulated approximately four times faster than at 20 degrees C. Heparin did not affect binding of the antibody to clots. To assess the feasibility of thrombus detection in vivo, an extracorporeal rat thrombus model was used. A thrombus in a shunt between a carotid artery and a jugular vein became visible 1 h after injection of the labelled Y22 and, more clearly, after 3 h.

Animals↗
PubMed1989

In vivo distribution and elimination of hemoglobin modified by intramolecular cross-linking with 2-nor-2-formylpyridoxal 5'-phosphate.

Modified hemoglobin solutions have potential application as plasma expanders with oxygen-transporting capacity. In a previous study it was found that modification of hemoglobin by intramolecular cross-linking with 2-nor-2-formylpyridoxal 5'-phosphate (NFPLP) improves the vascular retention time by a factor of three, and it also improves the oxygen-transporting properties. In the present study we investigated in rats how, after exchange transfusion of a clinically relevant dose, the modified hemoglobin (HbNFPLP) was distributed in the body compared with how the unmodified hemoglobin was distributed. By using a new technetium 99m labeling technique, we found in a scintigraphic study that accumulation of hemoglobin in the kidneys was greatly diminished by the intramolecular cross-linking with NFPLP. These findings were confirmed by light-microscopic observations after diaminobenzidine staining. It was concluded that the impairment of kidney function caused by blockade of the tubuli is not to be expected from HbNFPLP. In the liver and spleen, where the free HbNFPLP is possibly eliminated, some accumulation of 99mTc label was observed, but the major part of the extravascular label was diffusely spread throughout the body. This led to the conclusion that important accumulation of undegraded HbNFPLP does not occur in the liver and spleen. Rapid appearance of both hemoglobin and HbNFPLP in the lymph showed that cross-linking with NFPLP does not prevent the distribution of hemoglobin over the interstitial space in the first hours after administration. However, pharmacokinetic analysis demonstrated that transcapillary transfer contributes only to a limited extent to the disappearance from the circulation. During 24-hour infusions of HbNFPLP, a steady state with a constant plasma concentration was easily reached. The latter experiment indicated that the eliminating system does not become saturated during prolonged administration of large doses of HbNFPLP.

3,3'-Diaminobenzidine↗
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↗
PubMed1985

Uptake of 123I-5-iodo-2-thiouracil, a possible radiopharmaceutical for noninvasive detection of ocular melanoma, in melanotic and amelanotic melanomas in hamsters.

The uptake of 123I-5-iodo-2-thiouracil in melanotic and amelanotic melanoma implanted in Syrian golden hamsters was studied. A selective accumulation was found in the tumours. Uptake of 123ITU in melanotic melanomas was 4 to 5 times the uptake in amelanotic ones. For both tumours high ratios of tumours versus non-tumour were found. The high accumulation of 123ITU in both kinds of tumours and the high tumour versus non-tumour ratios suggest that 123ITU may be a promising radiopharmaceutical for the detection of ocular melanoma.

Animals↗
PubMed1984

In vitro stability of 99Tcm bone scan preparations from different manufacturers measured by various radiopharmaceutical parameters.

We have investigated the stability of 99Tcm-labelled kit preparations of the bone seeking agents methylene diphosphonate (MDP), hydroxymethylene diphosphonate (HDP) and dicarboxypropane diphosphonate (DPD). This was done by determining amounts of free 99Tcm pertechnetate under various experimental parameters. The radiopharmaceuticals were made with 100 and 300 mCi 99Tcm eluents and kept under the moderate condition of occasional inverting (1) or continuous rolling (2). Analysis took place 5 min, 2 h, 4 h and 6 h after preparation. In general free 99Tcm pertechnetate concentrations were less when 100 mCi 99Tcm eluent was used than with 300 mCi amounts. The level of impurity was also lower in vials kept under condition (1) than in vials kept under condition (2). Unexpected concentrations of free 99Tcm pertechnetate (maximum about 30%) were found in some commercial preparations. Only in one MDP and one HDP preparation did the average free 99Tcm pertechnetate concentration stay within tolerable limits under all experimental parameters. This study demonstrates that careful quality control is needed and that only freshly prepared bone-seeking radiopharmaceuticals should be applied, especially when 99Tcm eluents of about 300 mCi are used for kit preparation.

Bone and Bones↗