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J W Bulte

Publications and source records attributed to J W Bulte.

At least 37 records · Page 2Linked to original sources
PubMed1996

T1 and T2 of ferritin solutions: effect of loading factor.

Proton magnetic relaxation times T1 and T2 were measured at field strengths from 0.05 T to 1.5 T in solutions of ferritin with loading factors from 90 to 3600 iron atoms per molecule. 1/T2 increased linearly with field strength, as previously observed, and the slope per unit iron was approximately the same in all samples. This latter finding indicates that the field dependence of T2 may be used as a measure of ferritin-bound iron, regardless of loading factor. A possible explanation is presented, based on the presumed antiferromagnetic structure of the ferritin core and the linear dependence of 1/T2 on core magnetization. A nonzero contribution to 1/T2 in the limit of low field and a contribution to 1/T1 were also found, both of which increase linearly with loading factor for constant protein concentration; these effects represent quantum mechanical dipole-dipole relaxation of water protons either by iron atoms on the surface of the core or by the iron core itself. Finally, the extrapolated intercept at LF = 0 for both 1/T1 and 1/T2 indicates a contribution from a small number of iron ions bound to the protein shell. These results may help in the use of MRI to measure brain iron and possibly even ferritin loading factor.

Animals↗
PubMed1995

Magnetic resonance imaging of brain iron in health and disease.

Brain iron is a major contributor to magnetic resonance imaging (MRI) contrast in normal gray matter, and its role in the pathogenesis of different neurological disorders has also become apparent. Non-heme brain iron is present in the brain mainly in the form of ferritin. The unique magnetic properties of ferritin determine different signal changes on both T1- and T2-weighted images, and the T2 relaxation rates have a linear dependence on applied field strength. This finding is typical for ferric oxyhydroxide cores. The resulting T2-shortening also depends on echo-spacing used in the imaging sequence as well as on the water diffusion coefficient and the size of the ferritin cluster. Quantitation of non-heme brain iron by MRI aids in the diagnosis and monitoring of different neurological diseases.

Brain↗
PubMed1995

Initial assessment of magnetoferritin biokinetics and proton relaxation enhancement in rats.

RATIONALE AND OBJECTIVES: We evaluated the biokinetics and proton relaxation enhancement of magnetoferritin, a recently developed class of superparamagnetic iron oxides, in rats. METHODS: "Equine" magnetoferritin was administered intravenously at 5 mg protein and 1.4 mg Fe/kg in nude rats carrying subcutaneous xenografted human small-cell lung carcinoma with and without preinjection of 100 mg/kg equine apoferritin. Blood clearance, in vivo biodistribution, and proton relaxation enhancement were assessed by variable field relaxometry, immunohistochemistry, and magnetic resonance (MR) imaging at 1.5 T. RESULTS: Magnetoferritin clearance from blood followed biexponential kinetics, with a short initial half-life of 1.4-1.7 min. A second, longer component lasted for several hours. Histochemical staining, MR imaging, and ex vivo relaxometry revealed rapid uptake of magnetoferritin in the liver, spleen, and lymph nodes. There was no difference in biodistribution after apoferritin preinjection. CONCLUSION: In the rat, equine magnetoferritin is rapidly sequestered by cells of the reticuloendothelial system, with no direct involvement of ferritin receptors. These properties may allow the use of magnetoferritin as an MR contrast agent for the liver and spleen.

Animals↗
PubMed1994

Persistent oral contrast agent lining the intestine in severe mucosal disease: elucidation of radiographic appearance.

Plain radiographs and computed tomographic scans obtained in a severely neutropenic patient with acute lymphoblastic leukemia and cytomegalovirus-associated enterocolitis revealed a pattern of prolonged mucosal adherence of oral contrast agent to the small bowel. This pattern was seen as long as 16 weeks after administration of contrast agent and has been seen previously only in patients who have received bone marrow transplants. Two sets of intestinal biopsy specimens contained crystals that coated denuded mucosa at the site of ulceration and later were trapped within the lamina propria. Electron diffraction and energy-dispersive radiographic analysis showed that these crystals were composed of barium sulfate.

Administration, Oral↗
PubMed1993

Selective MR imaging of labeled human peripheral blood mononuclear cells by liposome mediated incorporation of dextran-magnetite particles.

Human peripheral blood mononuclear cells (PBMCs) were incubated with large unilamellar vesicles (LUV) containing encapsulated dextran-magnetite particles (DMP). This resulted in an efficient incorporation of DMP. Electron microscopy revealed the presence of DMP in cells mainly in phagosomes and secondary lysosomes. DMP-labeled PBMCs showed a strong increase of the transverse relaxation rate (up to 16.6 s-1 for 5 x 10(7) cells/ml) and, accordingly, a great loss of signal intensity in MR imaging. The fraction of DMP containing PBMCs could be enriched by magnetic cell separation. The major population of the DMP containing cells proved to be monocytes. When PBMCs depleted of monocytes were used for labeling, DMP uptake was observed also in the peripheral blood lymphocytes. The labeling of PBMCs presented here may be used in future studies of selective MR imaging of in vivo cell migration in a variety of immunologically compromised tissue states, e.g., tumors, transplantations, and abscesses.

Contrast Media↗
PubMed1993

Magnetite as a potent contrast-enhancing agent in magnetic resonance imaging to visualize blood-brain barrier disruption.

Imaging of blood-brain barrier damage by magnetic resonance was currently studied as to the potential of dextran-magnetite particles (DMP) for contrast enhancement. For that purpose, dextran-T10 (average molecular weight: 10.9 Kilodalton) was complexed with magnetite (Fe3O4) in ammonia. Experimental testing of the agent was made in vivo using Wistar rats with a freezing injury to the brain. DMP was i.v. injected at a dose of 90 microM Fe/kg b.w. followed by 2% Evans blue (0.6 ml). Control animals with trauma were studied without administration of DMP. Histochemical assessments were made to analyze the tissue distribution of DMP in the brain, kidney and liver after fixation in 4% formalin. MR imaging was conducted with 1.5 Tesla field strength with a circular coil 15 min after the freezing insult and administration of DMP. T1- and T2-weighted images were obtained using spin echo sequences among others. Regression analyses indicated a 50% reduction of T1 at a DMP concentration of 48 microM Fe, while for T2 only 4 microM/Fe(DMP) were sufficient for a 50% reduction. DMP was also accumulating in other organs, particularly in the Kupffer cells of the liver. Administration of DMP led to recognition of the freezing lesion as black area in agreement with macroscopical findings obtained by autopsy. In animals with a freezing lesion without administration of DMP, only T2-weighted images demonstrated a somewhat higher intensity attributable to the disruption of the blood-brain barrier. The present findings demonstrate the usefulness of DMP for contrast enhancement of lesions following disruption of the blood-brain barrier.

Animals↗
PubMed1993

Intracerebral and subcutaneous xenografts of human SCLC in the nude rat: comparison of monoclonal antibody localization and tumor infiltrating lymphocytes.

In the WAG/Rij nude rat, subcutaneous (s.c.) and intracerebral (i.c.) xenografts of the human SCLC cell line GLC-28 were evaluated for their growth behavior, in vivo monoclonal antibody binding and presence of tumor infiltrating lymphocytes. For the i.c. xenografts, two models of cerebral tumor growth were studied, one in the cerebral cortex and one in the lateral ventricle of the brain. In the s.c. and both i.c. xenografts models, in vivo localization of anti-carcinoma moab MOC-31 occurred within 4 hours after i.p. injection, with a maximal binding at 24 h after injection. A pronounced tumor infiltration of predominantly NK cells was observed for s.c. and intraventricular xenografts, but not for the GLC-28 tumors xenografted in the cerebral cortex. The presented nude rat/GLC-28 xenograft models may be used for the in vivo testing of experimental imaging techniques or alternative treatment strategies relevant to brain metastases of human SCLC.

Animals↗
PubMed1993

Our approach towards developing a specific tumour-targeted MRI contrast agent for the brain.

This review presents various aspects of the technological development, and their assessment in the design of a contrast agent for MRI, tailored to visualise tumours in the brain. First, it was demonstrated that magnetite as a contrast agent exhibited a much stronger relaxivity than gadolinium. The prepared magnetite particles bound to dextran, were also shown to be of appropriate size by electron microscopy. After their intravenous injection into rats with blood-brain barrier disruption, the lesion was strongly enhanced by T2-shortening. Furthermore, monoclonal antibodies directed against small cell lung carcinoma, proved to be able to penetrate into tumours, which had been raised by implantation of the small cell lung carcinoma cells into the brains of nude rats. As to the essential step, it was demonstrated in vitro that magnetite particles coupled to monoclonal antibodies by the biotin-streptavidin binding, could be bound to the target cells of the antibody, changing the relaxation rates of the latter. Finally it could be shown in vitro that an alternative approach, using lymphocytes to be targeted to tumour cells, also proved feasible, in that these lymphocytes could be labelled with magnetite that had been incorporated into liposomes. Further developments will be the in vivo assessment of the acquired progress in experimental animals, before clinical application is warranted.

Animals↗
PubMed1993

Radioimmunodetection of human small cell lung carcinoma xenografts in the nude rat using 111in-labelled monoclonal antibody MOC-31.

The applicability of mouse monoclonal antibody MOC-31 for in vivo radioimmunodetection of human small cell lung cancer (SCLC) was investigated in a nude rat xenograft model. MOC-31 is reactive with a 38 kD pancarcinoma membrane antigen. [111In]DTPA-MOC-31 showed good in vivo immunolocalisation to xenografted SCLC cells, whereas antigen-related uptake was low in normal rat tissues and in a control antigen-negative, human-derived tumour. Non-antigen-related uptake in the liver could be blocked by pretreatment with irrelevant antibody. It is concluded that MOC-31 can be used for radioimmunodetection of SCLC in vivo and may be suitable as a targeting device in patients.

Animals↗
PubMed1992

Dextran-magnetite particles: contrast-enhanced MRI of blood-brain barrier disruption in a rat model.

Dextran-magnetite particles (DMP) were studied for their use as a MR contrast agent to visualize lesions with a blood-brain barrier (bbb) disruption. A freezing injury to the rat cerebral cortex was used as a model of bbb disruption. The biodistribution of iv-injected DMP was studied using atomic absorption spectrophotometry, electron microscopy, and MRI. One hour after injection, focal accumulation of the particles in capillary endothelial cells could be demonstrated in the freezing lesion. Despite the observation that the relaxivity of DMP in vivo appears to be less well pronounced than that in vitro, the MR imaging studies show that DMP can be used to visualize bbb disruption with adequate contrast.

Animals↗
PubMed1992

Specific MR imaging of human lymphocytes by monoclonal antibody-guided dextran-magnetite particles.

Human lymphocytes were labeled with biotinylated anti-lymphocyte-directed monoclonal antibodies, to which streptavidin and subsequently biotinylated dextran-magnetite particles were coupled. This labeling resulted in a strong and selective negative contrast enhancement of lymphocyte suspensions at 2.0 T, caused predominantly by the specific increase of R2 with a small but significant specific increase of R1. The R1 was found to decrease with increasing field strength. The immunolabeling procedure described here may be used for the selective signal depletion of target cells in MR imaging.

Antibodies, Monoclonal↗
PubMed1990

Passage of DMP across a disrupted BBB in the context of antibody-mediated MR imaging of brain metastases.

To study the possible application of monoclonal antibody/dextran-magnetite conjugates in specific MR imaging of brain metastases, both components of these conjugates were tested for their ability to penetrate the endothelium during conditions of local blood-brain barrier (BBB) impairment. The passage of dextran-magnetite particles (DMP) across a disrupted blood-brain barrier was studied in a freezing lesion model using electron microscopy (EM) and MR imaging. One hour after i.v. injection, focal accumulation of DMP in capillary endothelial cells within the freezing lesion was shown by EM. In parallel with this, MR imaging indicated a strong contrast enhancement in the lesion. EM observations showed that the particles were still present in the endothelial cells four and eight hours after injection. The passage of an anti-small cell lung cancer (SCLC) monoclonal antibody across the endothelium of intracerebrally xenografted human SCLC was studied using immunohistological techniques. It was found that passage across endothelial cell occurred in the tumor within four hours after injection.

Animals↗
PubMed1988

Monoclonal antibody JSB-1 detects a highly conserved epitope on the P-glycoprotein associated with multi-drug-resistance.

Resistance to multiple chemotherapeutic agents is a common clinical problem in the treatment of cancer. This resistance may occur before primary therapy or be acquired during treatment. We have generated a monoclonal antibody (MAb) (JSB-I), specific for a conserved epitope on the plasma membrane 170- to 180-kDa glycoprotein, the expression of which is strongly correlated with the degree of multi-drug resistance (MDR). JSB-I strongly binds to both Chinese-hamster-derived MDR cell lines and human MDR cell lines, including cell lines derived from lung and ovary. A drug-sensitive revertant line, and the corresponding drug-sensitive parent lines, showed only weak reactivity or none at all. JSB-I reacts strongly to air-dried or acetone-fixed cells and therefore has potential value for diagnostic detection of MDR cells in human tumor samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Frequency dependence of MR relaxation times. I. Paramagnetic ions.

T1 and T2 of paramagnetic ions in free and chelated form were measured over the range of clinical magnetic resonance imaging field strengths (0.02-1.5 T). T1 values agreed with published data; however, to our knowledge, the field dependence of T2 has not been systematically studied before Mn2+, Cr3+, and Fe3+ all showed T2 reduction at high field strengths, although reduction due to Fe3+ was minimal. This is believed to be due to "contact" interactions, which have been previously noted for manganese. No such T2 reduction was seen in the chelates, except that dysprosium chelate (but not free ion) showed an anomalous decrease in T2 at high field strengths, which may possibly be explained by a dephasing effect caused by the large magnetic moment of Dy3+.

Chromium↗
PubMedDate not supplied

Frequency dependence of MR relaxation times. II. Iron oxides.

The frequency dependence of T1 and T2 was measured for homogeneous suspensions of magnetite and iron oxyhydroxide particles in water with various concentrations of gelatin. The transverse relaxivity showed two types of behavior: (a) For magnetic particles, there was a rapid increase in T2 relaxivity with frequency, followed by a saturation plateau, which accorded with the Langevin magnetization function. From these curves, the magnetic moment of the particle domains was estimated to range from 0.8 to 6.3 x 10(4) Bohr magnetons. (b) For iron oxyhydroxide (ferritin, ferrihydrite, and akaganéite) particles, T2 relaxivity increased linearly with frequency, the slope of the increase characteristic for each particle. T2 relaxivity generally increased with increasing gelatin concentration, corresponding to the measured decrease in the water diffusion coefficient. For iron oxides, homogeneously distributed either as iatrogenic agents or endogenous biominerals, these findings may aid in the interpretation of in vivo relaxivity and the effect on MR imaging.

Contrast Media↗
PubMedDate not supplied

Magnetoferritin: characterization of a novel superparamagnetic MR contrast agent.

A protein-encaged superparamagnetic iron oxide has been developed and characterized by using horse spleen apoferritin as a novel bioreactive environment. The roughly spherical magnetoferritin molecules, 120 A in diameter, are composed of a monocrystalline maghemite or magnetite core 73 A +/- 14 in diameter. Except for the additional presence of iron-rich molecules of higher molecular weight, the appearance and molecular weight (450 kd) of magnetoferritin are identical to that of natural ferritin; the molecules are externally indistinguishable from their precursor, with a pI (isoelectric point) in the range 4.3-4.6. The measured magnetic moment of the superparamagnetic cores is 13,200 Bohr magnetons per molecule, with T1 and T2 relaxivities (r1 and r2) of 8 and 175 L.mmol-1 (Fe).sec-1, respectively, at body temperature and clinical field strengths. The unusually high r2/r1 ratio of 22 is thought to arise from ideal core composition, with no evidence of crystalline paramagnetic inclusions. T2 relaxation enhancement can be well correlated to the field-dependent molecular magnetization, as given by the Langevin magnetization function, raised to a power in the range 1.4-1.6. With its nanodimensional biomimetic protein cage as a rigid, convenient matrix for complexing a plethora of bioactive substances, magnetoferritin may provide a novel template for specific targeting of selected cellular sites.

Animals↗