Secretome of apoptotic peripheral blood cells (APOSEC) attenuates microvascular obstruction in a porcine closed chest reperfused acute myocardial infarction model: role of platelet aggregation and vasodilation.

Although epicardial blood flow can be restored by an early intervention in most cases, a lack of adequate reperfusion at the microvascular level is often a limiting prognostic factor of acute myocardial infarction (AMI). Our group has recently found that paracrine factors secreted from apoptotic peripheral blood mononuclear cells (APOSEC) attenuate the extent of myocardial injury. The aim of this study was to determine the influence of APOSEC on microvascular obstruction (MVO) in a porcine AMI model. A single dose of APOSEC was intravenously injected in a closed chest reperfused infarction model. MVO was determined by magnetic resonance imaging and cardiac catheterization. Role of platelet function and vasodilation were monitored by means of ELISA, flow cytometry, aggregometry, western blot and myographic experiments in vitro and in vivo. Treatment of AMI with APOSEC resulted in a significant reduction of MVO. Platelet activation markers were reduced in plasma samples obtained during AMI, suggesting an anti-aggregatory capacity of APOSEC. This finding was confirmed by in vitro tests showing that activation and aggregation of both porcine and human platelets were significantly impaired by co-incubation with APOSEC, paralleled by vasodilator-stimulated phosphoprotein (VASP)-mediated inhibition of platelets. In addition, APOSEC evidenced a significant vasodilatory capacity on coronary arteries via p-eNOS and iNOS activation. Our data give first evidence that APOSEC reduces the extent of MVO during AMI, and suggest that modulation of platelet activation and vasodilation in the initial phase after myocardial infarction contributes to the improved long-term outcome in APOSEC treated animals.

Generation of individualized thalamus target maps by using statistical shape models and thalamocortical tractography.

BACKGROUND AND PURPOSE: Neurosurgical interventions of the thalamus rely on transferring stereotactic coordinates from an atlas onto the patient's MR brain images. We propose a prototype application for performing thalamus target map individualization by fusing patient-specific thalamus geometric information and diffusion tensor tractography. MATERIALS AND METHODS: Previously, our workgroup developed a thalamus atlas by fusing anatomic information from 7 histologically processed thalami. Thalamocortical connectivity maps were generated from DTI scans of 40 subjects by using a previously described procedure and were mapped to a standard neuroimaging space. These data were merged into a statistical shape model describing the morphologic variability of the thalamic outline, nuclei, and connectivity landmarks. This model was used to deform the atlas to individual images. Postmortem MR imaging scans were used to quantify the accuracy of nuclei predictions. RESULTS: Reliable tractography-based markers were located in the ventral lateral thalamus, with the somatosensory connections coinciding with the VPLa and VPLp nuclei; and motor/premotor connections, with the VLpv and VLa nuclei. Prediction accuracy of thalamus outlines was higher with the SSM approach than the ACPC alignment of data (0.56 mm versus 1.24; Dice overlap: 0.87 versus 0.7); for individual nuclei: 0.65 mm, Dice: 0.63 (SSM); 1.24 mm, Dice: 0.4 (ACPC). CONCLUSIONS: Previous studies have already applied DTI to the thalamus. As a further step in this direction, we demonstrate a hybrid approach by using statistical shape models, which have the potential to cope with intersubject variations in individual thalamus geometry.

Clinical, radiological and pathological correlates of leukoaraiosis.

INTRODUCTION: Leukoaraiosis is characterized by an abnormal appearance of the brain white matter on imaging. Its pathogenesis is still a matter of investigation. The purpose of this study was to investigate the radiological, clinical and pathological correlates of leukoaraiosis. METHODS: The study population consisted of 93 deceased patients. The pre-mortem T2W magnetic resonance images were evaluated for the presence and grading of leukoaraiosis. The clinical and pathological characteristics based on the clinical charts and autopsy reports were evaluated. Tissue specimens of the blocks of 19 brains that demonstrated severe leukoaraiosis and those of five control brains were excised and stained. RESULTS: The variables found to be significantly associated with leukoaraiosis were age and a clinical history of Parkinson's disease. Other risk factors and pathological markers of atherosclerosis were not significantly correlated with leukoaraiosis. No significant difference was found between the scoring of the myelin integrity, glial fibrillary acidic protein, cluster of differentiation 68 and smooth muscle actin. There was a significant difference with respect to thickening of vessels walls. CONCLUSIONS: Our pathological results indicate that structural vascular abnormalities characterized by vessel wall thickening are associated with leukoaraiosis, supporting the assertion that vascular changes and ischemia generate leukoaraiosis. The relations between parkinsonism and leukoaraiosis may be explicable through vascular effects on the circuitry of the basal ganglia.

Antiproliferative effect of 4-thiouridylate on OCM-1 uveal melanoma cells.

PURPOSE: Brachytherapy is a well-established, effective treatment for uveal melanoma with a failure rate of 15%. The fatal consequence of unsuccessful treatments offers reason for improvement of the method. The authors propose using an apoptosis inducing agent locally, concomitantly with the well-established therapy, to sensitize the tumor cells. The authors propose a new nontoxic moderately active apoptosis inducing agent, 4-thio-uridylate (s4UMP), for this purpose. METHODS: OCM-1 uveal melanoma cells were treated with various concentrations of s4UMP and its effect was monitored by measuring the cell viability (MTT assay). The following apoptosis detecting methods were performed to reveal the mechanism of decreased cell viability: light microscopy, DNA fragmentation assay, determination of caspase 9 activity, and FACS analysis. RESULTS: The viability of uveal melanoma cells was decreased by 32%, 40%, and 9% after 24, 48, and 72 hours of treatment with 10 microg/mL (30 microM) s4UMP. The effect was not dose dependent; it rather followed a saturation-type inhibition and the cells at lower drug concentration recovered after 72 hours. Characteristic apoptotic cell morphology and DNA fragmentation was detected in treated cells. The caspase-9 was activated upon treatment showing maximal activity at 48 hours suggesting the induction of apoptosis. The annexin binding activity further verified the apoptogenic activity of s4UMP. CONCLUSIONS: Uveal melanoma, more than other solid tumors, is resistant to most of the chemotherapeutic protocols as indicated by the high mortality rate of metastatic disease. The authors showed that s4UMP, a naturally occurring nucleotide, could induce apoptosis in uveal melanoma cells, suggesting a potential supplementary therapeutic application of the compound.

Antiproliferative effect of 4-thiouridylate on OCM-1 uveal melanoma cells.

PURPOSE: Brachytherapy is a well-established, effective treatment for uveal melanoma with a failure rate of 15%. The fatal consequence of unsuccessful treatments offers reason for improvement of the method. The authors propose using an apoptosis inducing agent locally, concomitantly with the well-established therapy, to sensitize the tumor cells. The authors propose a new nontoxic moderately active apoptosis inducing agent, 4-thio-uridylate (s4UMP), for this purpose. METHODS: OCM-1 uveal melanoma cells were treated with various concentrations of s4UMP and its effect was monitored by measuring the cell viability (MTT assay). The following apoptosis detecting methods were performed to reveal the mechanism of decreased cell viability: light microscopy, DNA fragmentation assay, determination of caspase 9 activity, and FACS analysis. RESULTS: The viability of uveal melanoma cells was decreased by 32%, 40%, and 9% after 24, 48, and 72 hours of treatment with 10 g/mL (30 M) s4UMP. The effect was not dose dependent; it rather followed a saturation-type inhibition and the cells at lower drug concentration recovered after 72 hours. Characteristic apoptotic cell morphology and DNA fragmentation was detected in treated cells. The caspase-9 was activated upon treatment showing maximal activity at 48 hours suggesting the induction of apoptosis. The annexin binding activity further verified the apoptogenic activity of s4UMP. CONCLUSIONS: Uveal melanoma, more than other solid tumors, is resistant to most of the chemotherapeutic protocols as indicated by the high mortality rate of metastatic disease. The authors showed that s4UMP, a naturally occurring nucleotide, could induce apoptosis in uveal melanoma cells, suggesting a potential supplementary therapeutic application of the compound.

Brain water and proton magnetic resonance relaxation in preterm and term rabbit pups: their relation to tissue hyaluronan.

The present study was performed to investigate simultaneously total brain water, T1 and T2 relaxation times, and hyaluronan (HA) in fetal and neonatal rabbits. Attempts were also made to establish the relationship of HA to total brain water and to T2-derived motionally distinct water fractions, since HA is known to bind water and to limit tissue water mobility. Experiments were carried out in fetal Pannon white rabbit pups at gestational ages of 25, 27, 29, and 31 days and at a postnatal age of 4 days. The brain tissue water content (desiccation method), T1 and T2 relaxation times (H1-NMR method), and HA concentration (radioassay HA 50) were measured, and free and bound water fractions were calculated by using multicomponent fits of the T2 relaxation curves. Compared with values in newborn pups, water and HA contents were found to be highly elevated in the preterm brain and decreased markedly during early postnatal life. The trends and time courses of T1 and T2 relaxation times proved to be similar, but the postnatal decrease in T2 was preceded by a significant decline in late gestation. Maturity-related changes occurred in the T2 relaxation derived bound water fraction which amounted to 4-19% of brain water. The bound water fraction appeared to be independent of total brain water and HA concentration, and HA is, therefore, unlikely to be the only factor controlling brain water mobility. The clear dissociation of bound water fraction from total water suggests restructuring of brain water during the perinatal period.

Lung water and proton magnetic resonance relaxation in preterm and term rabbit pups: their relation to tissue hyaluronan.

The present study was performed to investigate simultaneously total lung water, T(1) and T(2) relaxation times, and hyaluronan (HA) in preterm and term rabbits. Attempts were also made to establish the relationship of HA to total lung water and to T(2)-derived motionally distinct water fractions. Experiments were performed in fetal Pannon white rabbit pups at gestational ages of 25, 27, 29, and 31 d and at a postnatal age of 4 d. Lung tissue water content (desiccation method), T(1) and T(2) relaxation times (H(1)-NMR method), and HA concentration (radioassay) were measured, and free and bound water fractions were calculated by using multicomponent fits of the T(2) relaxation curves. Lung water content and T(1) and T(2) relaxation times were highest at a gestational age of 27 d and then declined steadily during the whole study period. Similar trends and time courses were seen for the fast and slow components of the T(2) relaxation curve. The T(2)-derived free water fraction remained unchanged at a gestational age of 25-29 d ( approximately 67%), but increased progressively to a value of 78.5 +/- 7.9% at 31 d (p < 0. 001) and to 83.4 +/- 9.4% at the postnatal age of 4 d (p < 0.01). Opposite changes occurred in the bound water fraction. Lung HA concentration decreased with advancing gestation from 870.8 +/- 205.2 microg/g dry weight at 25 d to 162.6 +/- 32.4 microg/g dry weight at 31 d (p < 0.001), but it was increased 2-fold postnatally. HA correlated positively with total lung water (r = 0.39; p < 0.001) but not with the bound water fraction. It is suggested that the physiologic lung dehydration is associated with macromolecule-related reorganization of lung water and that the role of HA in this process needs to be further investigated.

[Chiari I. malformation, a new childhood disease?]. / Chiari I. malformáció, egy "új" gyermekbetegség?

From July 1, 1994 to July 1, 1997 a total of 17 children with Chiari I malformation diagnosed by MRI was seen in our hospital. Six of them underwent craniocervical decompression and tonsilar resection. The major complaints of all these children were gait ataxia and persisting (longer than 6 month) headache, and one child had acutely presenting vertigo and problem of swallowing. The MRI showed that in all cases the tonsils were displaced below the level of CI. Hydrocephalus or syrinx was not seen. At surgery the tonsils were resected. All the patients can be considered cured and symptom free at an average follow up of 13 month.

[Refsum disease]. / Refsum-kór.

For the first time in literature the authors interpret the pathography of Refsum's disease, in the case of their patient, as pseudo-hypervitaminosis A. The biochemical basis of the clinical picture is a defect in the activity of phytanic-acid-alpha-hydrolase belonging to the peroxisomal system. As a consequence, phytanic acid accumulates in the serum and in the parenchymal tissues. Retinol, an alcohol with high molecular weight, is a natural ligand of nuclear RXR (retinoid-X-receptor), which plays an important role in the regulation of peroxisoma synthesis. In Refsum's disease the phytanic acid accumulated because of the enzyme defect competes with the biotransformation derivates (all-trans-retinoic acid, 9-cis-retinoic acid) of the all-trans-retinol (vitamin A) for the nuclear RX receptor binding sites, and as a very potent receptoractivator it causes the intestinal symptoms of hypervitaminosis A. The authors review the procedure of fatty-acid chromatography necessary for the establishment of the diagnosis and discuss--in addition to dietary restrictions--recent therapeutic possibilities, like plasmapheresis, cascade filtration, lipapheresis and oral batylalcohol treatment.

[Dynamic MR examination of the breast--histological correlations]. / Az emló dinamikus MR-vizsgálata--szövettani korreláció.

The authors outline dynamic MR mammography (dMRM) as a highly sensitive diagnostic method for the examination of the breast. In a retrospective study relating to 84 processed cases, in the knowledge of the cytological-histological findings the diagnostic accuracy of the examinations was determined. The role of the method in detecting benign and malignant changes of the breast has been estimated. Misdiagnosed cases have been analysed and recommendations for the application of the method are included. The MR proved to be positive in 32 cases and negative in 3 cases of the analysed 35 malignant tumors. Benign lesions were found at microscopy in 49 cases, of which MR correctly diagnosed 40. The sensitivity and the specificity of dynamic MR mammography were 91% and 82%.

Brain adaptation to water loading in rabbits as assessed by NMR relaxometry.

The present study was undertaken to investigate the cerebral adaptation to hypoosmolar stress in adult Pannon white rabbits by applying proton nuclear magnetic resonance relaxometry. Progressive hyponatremia was induced by combined administration of hypotonic dextrose in water and 8-deamino-arginine vasopressin over a hydration period of 3, 24, and 48 h. Each group comprised five animals. After completing the hydration protocols, blood was taken to determine plasma osmolality (freezing point depression) and sodium concentration (ion-selective electrode) and, at about the same time, T2-weighted images were made. After the in vivo measurements, the animals were killed and brain tissue samples were obtained to measure water content (desiccation method) and T1 and T2 relaxation times (proton nuclear magnetic resonance method). Free and bound water fractions were calculated by using multicomponent fits of the T2 relaxation curves. It was shown that brain water content and T1 relaxation time remained unchanged despite the progressing hyponatremia. By contrast, T2 relaxation time increased steadily from the control value of 100.2 +/- 7.7 ms to attain its maximum of 107.5 +/- 8.5 ms (p < 0.05) after 48 h of hydration. Using biexponential analysis, fast and slow components of the T2 relaxation curve could be distinguished that corresponded to the bound (T21) and free (T22) water fractions. In response to hyponatremia, the bound water fraction was markedly depressed from 6.5 +/- 3.0% to 3.6 +/- 0.9% (3 h, p < 0.05) and 3.9 +/- 0.8% (24 h, p < 0.05); then it approached the initial value of 5.3 +/- 2.5% by the end of the hydration period of 48 h. It is concluded that restructuring of brain water is a contributory factor to the successful adaptation to hypotonic environment.

In vivo assessment of breast muscle, abdominal fat and total fat volume in meat-type chickens by magnetic resonance imaging.

Measurements were performed on commercial broiler chickens by magnetic resonance imaging (MRI) tomography. A total of 72 chickens were scanned at the age of 6, 7, 8, 10, 16 and 20 weeks. MRI scans based on spin echo sequence were taken in the three orthogonal planes. The volume of the pectoral muscles increased from 259 cm3 to 1035 cm3 in males and from 250 cm3 to 875 cm3 in females between 6 and 20 weeks of age. Abdominal fat volume increased from 18.9 cm3 to 153.2 cm3 in males and from 19.3 cm3 to 267.0 cm3 in females between 7 and 20 weeks of age. Total body fat volume increased from 129 cm3 to 557 cm3 in males and from 171 cm3 to 1321 cm3 in females between 6 and 20 weeks of age. The correlation coefficients between the total volume of fat pixels and the amount of abdominal fat determined in the coronal plane by MRI were 0.85 and 0.95 in the male and female sex, respectively. Changes found in the pectoral muscles (mm. pectorales) as well as in total and abdominal fat volume were in close agreement with dissection data obtained at the slaughterhouse and with laboratory data based on the measurement of total body chemical composition in both sexes. This MRI method can be a good complement to computed tomography (CT) scanning in the transversal plane.

Water content and proton magnetic resonance relaxation times of the brain in newborn rabbits.

The present study, using proton nuclear magnetic resonance relaxation (H1 NMR) measurements, was undertaken to quantitate water fractions with different mobility in the brain tissue obtained form New Zealand White rabbit pups. Serial studies were carried out at the postnatal age of 0-1, 24, 48, 72, and 96 h in pups nursed with their mothers and suckling ad libitum (group I) and in those pups separated from their mothers and completely withheld from suckling (group II). Tissue water content (desiccation method) and T1 and T2 relaxation times (H1 NMR method) were measured. Free, loosely bound, and tightly bound water fractions were calculated by applying multicomponent fits of the T2 relaxation curves. It was demonstrated that brain water content and T1 and T2 relaxation times did not change with age in the suckling pups. In pups withheld from suckling brain water decreased from 89.4 +/- 0.5% at birth to 87.7 +/- 0.1% at the age of 96 h (p < 0.05), T1 remained unchanged, and there was a significant fall in T2 by the age of 72 h (188 +/- 12 versus 178 +/- 4 ms, p < 0.05) and 96 h (171 +/- 6 ms, p < 0.01). Partition of brain water into bound and free fractions as derived from biexponential fits of T2 decay curve showed that the percent contribution of bound water fraction in pups of group I fell progressively from 61% at birth to 3% at the age of 72-96 h (p < 0.05). This fall was accelerated by the complete deprival of fluid intake, and the level of about 4% could be attained as early as the age of 24 h. Triexponential analysis of T2 relaxation curves revealed that the loosely bound fraction (middle component) predominated over the free (slow component) and the tightly bound (fast component) water fractions. In response to withholding fluid intake, the free water fraction increased 4-fold at the expense of tightly bound brain water. It is concluded that the majority of neonatal brain water is motion-constrained. The free, the loosely bound, and the tightly bound water fractions appear to be interrelated; from the brain water store water can be released to supply free water for volume regulation.

[Principles of functional MRI imaging and its possibilities in the study of cerebral cortex activation]. / A funkcionális MR képalkotás elve és lehetöségei a kérgi aktivációk vizsgálatában.

While MR imaging of anatomic structures has long been widely appreciated, the emergence of functional magnetic resonance imaging (FMRI) methods for localising brain activity has emerged in the beginning of the 90s. This new MRI technique produces images of activated brain regions by detecting the indirect effects of neural activity on local blood volume, flow and oxygen saturation, and it is a promising new tool for further understanding of the relationships among brain structure, function and pathology. The information revealed by FMRI is partially overlapping with PET and SPECT, but it is non-invasive and has a better spatial and temporal resolution. The authors briefly summarise the concept and basics of FMRI and demonstrate the first successful FMRI examination performed in Hungary. The potential role of FMRI in the clinical practice is presented.

[Method and use of intracranial cine MR imaging]. / Intracranialis mozgóképes magmágneses rezonanciás vizsgálatok és alkalmazásaik.

The authors introduce a dynamic, non-invasive MR method for the examination of liquorspaces and liquor flow in 221 patients. This method is suitable not only for a dynamic imaging of liquor-flow but also for the semi-quantitative evaluation of flow through the aqueduct. This later measurement can help to select the shuntresponsive NPH cases as well. Cine MR examination along with the routine protocol seems to be most helpful in the differential-diagnostics of different hydrocephalus cases.

Postnatal changes in water content and proton magnetic resonance relaxation times in newborn rabbit tissues.

In the present study, using proton nuclear magnetic resonance relaxation (H1 NMR) measurements, an attempt was made to quantitate water fractions with different mobility in the skin, skeletal muscle, and liver tissues obtained from New Zealand white rabbit pups. Serial studies were carried out at the postnatal age of 0-1, 24, 48, and 72 h in pups nursed with their mothers and suckling ad libitum (group I) and in those pups separated from their mothers and completely withheld from suckling (group II). Tissue water content (desiccation method) and T1 and T2 relaxation times (H1 NMR method) were measured. Free, loosely bound, and tightly bound water fractions were calculated by applying multicomponent fits of the T2 relaxation curves. It was demonstrated that skin water content and T1 and T2 relaxation times decreased with age (p < 0.01), the decrease in T2 proved to be more pronounced in group II than in group I (p < 0.05). Muscle and liver water, and T1 and T2 relaxation times did not change with age in the suckling pups. In response to with-holding fluid intake muscle water remained constant, liver water increased paradoxically (p < 0.05). T1 relaxation time showed no consistent change in either tissues, whereas T2 relaxation time decreased significantly (muscle, p < 0.01) or tended to decrease (liver, p < 0.06). Using biexponential analysis fast and slow components of T2 relaxation curve could be distinguished that corresponded to the bound and free water fractions. Bound water accounted for 42-47%, 50-57%, and 34-40% of total tissue water in the skin, skeletal muscle, and liver, respectively, regardless of age and fluid intake. Triexponential fits of the T2 relaxation curve made possible the further partition of tissue water into tightly bound (fast component), loosely bound (middle component), and free (slow component) water fractions. In all tissues studied, loosely bound fraction predominated (skin, 48-64%; muscle, 54-65%; liver, 45-63%), followed by the free (skin, 26-45%; muscle, 23-32%; liver, 20-25%) and the tightly bound water fraction (skin, 6-14%; muscle, 10-16%; liver, 14-33%). Postnatal age and fluid intake had no apparent influence on this pattern of distribution. It is concluded that the majority of neonatal tissue water is motion-constrained. The free, the loosely bound, and the tightly bound water fractions appear to be interrelated and dependent on age, fluid intake, the tissues studied, and their hydration.

Nuclear magnetic resonance relaxation parameters of muscle in malignant hyperthermia-susceptible swine.

RATIONALE AND OBJECTIVES: The malignant hyperthermia (MH) syndrome involves characteristic changes in metabolism that have a significant effect on the postmortem properties of muscle tissue. We investigated the 1H nuclear magnetic resonance (MR) relaxation parameters of muscle tissue from normal (MH-) and malignant hyperthermia-susceptible (MH+) swine taken before their death to identify whether postmortem metabolic differences would be accompanied by changes in relaxation parameters. METHODS: Muscle samples from 63 MH-susceptible swine were characterized by proton MR relaxation times (T1 and T2). The water content, pH, conducting, and the "subjective meat" quality were assessed in order to differentiate the meat into one of three groups: normal, pale-soft-exudative, and dark-firm-dry. RESULTS: The T2 relaxation of MH- and MH+ muscles was significantly different, but no significant changes were detected in the water content and corresponding T1 relaxation times. CONCLUSION: These data suggest that MH-susceptible swine can be distinguished from normal swine using nuclear MR relaxometry. The results of relaxation measurements and the multiexponential analysis of the T2 curves suggest a shift between the different water compartments during MH that might predict the increased water loss of muscle tissue after death.

[The Hungarian nifedipines]. / A magyar nifedipin.

The short history of the nifedipine drug substance containing Cordaflex product family--produced by EGIS Pharmaceuticals Ltd.--is presented.

Cation distribution in mammalian red blood cells: interspecies and intraspecies relationships between cellular ATP, potassium, sodium and magnesium concentrations.

The intracellular K+/Na+ ratio of erythrocytes of different mammalian species are known to differ markedly. These differences are sustained despite plasma potassium and sodium concentrations being almost identical, i.e. high [Na+] and low [K+], in all mammalian species. Conventional cell theory couples intracellular K+ and Na+ concentrations with Na+/K(+)-dependent ATPase activity. Ling's Association-Induction (AI) hypothesis couples intracellular K+ and Na+ concentrations with the concentration of ATP, by way of an inductive adsorption of both monovalent cations on the available terminal and lateral carboxyl groups of proteins. Based on the working hypothesis, different relationships are expected between the erythrocyte K+ and Na+ concentrations and ATP levels. Our results indicate that the intracellular ATP level in erythrocytes of different species corresponds with intracellular K+ and Na+ levels, K+/Na+ ratios and total K+ + Na+ levels. Similar relationships were revealed between the erythrocyte ATP and monovalent cation contents of different individual sheep.

Relaxometry, animal biodistribution, and magnetic resonance imaging studies of some new gadolinium (III) macrocyclic phosphinate and phosphonate monoester complexes.

The Gd3+ complexes of three new phosphorus containing tetraaza macrocycles (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene ethylphosphonic acid), H4DOTEP; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene phosphonic acid monoethylester), H4DOTPME; and the corresponding n-butyl ester, H4DOTPMB) were prepared and examined for possible use as MRI contrast agents. Although thermodynamically and kinetically less stable than Gd(DOTA)- in saline and HSA solution, the stability of these new macrocyclic complexes appears to be sufficiently high for in vivo applications. NMRD relaxivity profiles of the three complexes indicate that the number of inner sphere water molecules for these chelates is < or = 1 and that the more hydrophobic chelate, Gd(DOTPMB), binds to human serum albumin (HSA). Biodistribution studies of the radioactive 153Sm or 159Gd chelates in rats, gamma imaging of the 153Sm chelates in rats, and proton MRI studies of the nonradioactive Gd3+ chelates in rabbits all indicate that the DOTPMB complexes accumulate preferentially in the liver, spleen, and small intestines while the more hydrophilic DOTEP and DOTPME complexes appear to display renal clearances similar to other low molecular weight contrast agents.