Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “macrocycles”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources
PubMed2002

Threefold symmetric trimetallic macrocycles formed via the Weak-Link Approach.

The synthesis and characterization of a new threefold symmetric hemilabile phosphino-alkylthioether ligand are described. This ligand can be used in combination with Rh(I) and Ir(I) precursor complexes to prepare 40-membered macrocyles with threefold symmetry via the Weak-Link Approach. Synthesis and characterization of two such structures are reported along with a single crystal x-ray diffraction analysis of one of the key intermediates in the case of Rh(I). This is a demonstration of the viability of the Weak-Link Approach for preparing structures other than bimetallic macrocycles and suggests that it could be generalized for a wide range of higher symmetry structures through appropriate hemilabile ligand design.

Crystallography, X-Ray↗
PubMed1983

pH regulation of divalent/monovalent Ca/K cation transport selectivity by a macrocyclic carrier molecule.

The lipophilic dicarboxylic acid-dicarboxamide macrocycle 1 is an efficient carrier for calcium and potassium transport through a liquid membrane. The process involves competitive Ca2+/K+ symport coupled to proton antiport in a pH gradient. It presents a very pronounced phenomenon of pH regulation of transport selectivity from preferential K+ transport to preferential Ca2+ transport as the pH increases from 2 to 9 in the starting aqueous phase containing the metal ions. The results demonstrate how carrier design allows control of the rate and selectivity of divalent/monovalent M2+/M+ cation transport.

Calcium↗
PubMed1990

Biosynthesis of vitamin B12: isolation of precorrin-6x, a metal-free precursor of the corrin macrocycle retaining five S-adenosylmethionine-derived peripheral methyl groups.

delta-Aminolevulinic acid and trimethylisobacteriochlorin are converted by cell-free protein preparations from Pseudomonas denitrificans into a metal-free pigment, precorrin-6x. This pigment, which accumulates when the cell-free system lacks NADPH, can be enzymically converted in high yield (greater than 50%) into hydrogenobyrinic acid by the complete enzyme preparation. Double-labeling experiments establish that precorrin-6x carries five C-methyl groups, which appear at C-1, C-2, C-7, C-12 alpha, and C-17 of the hydrogenobyrinic acid formed enzymically from precorrin-6x. This precursor of the corrin macrocycle is at the dehydrocorrin level of oxidation, has undergone ring contraction and extrusion of C-20, but still carries the acetic acid side chain at C-12. It is demonstrated that the conversion of precorrin-6x into hydrogenobyrinic acid specifically requires an NADPH-dependent reduction step.

Magnetic Resonance Spectroscopy↗
PubMed1993

Molecular basis for the inhibition of human alpha-thrombin by the macrocyclic peptide cyclotheonamide A.

The macrocyclic peptide cyclotheonamide A (CtA), isolated from the marine sponge Theonella sp., represents an unusual class of serine protease inhibitor. A complex of this inhibitor with human alpha-thrombin, a protease central to the bioregulation of thrombosis and hemostasis, was studied by x-ray crystallography. This work (2.3-A resolution) confirms the structure of CtA and reveals intimate details about its molecular recognition within the enzyme active site. Interactions due to the "Pro-Arg motif" (Arg occupancy of the S1 specificity pocket; formation of a hydrogen-bonded two-strand antiparallel beta-sheet with Ser214-Gly216) and the alpha-keto amide group of CtA are primarily responsible for binding to thrombin, with the alpha-keto amide serving as a transition-state analogue. A special interaction with the "insertion loop" of thrombin (Tyr60A-Thr60I) is manifested through engagement of the hydroxyphenyl group of CtA with Trp60D as part of an "aromatic stacking chain." Biochemical inhibition data (Ki values at 37 degrees C) were obtained for CtA with thrombin and a diverse collection of serine proteases. Thus, CtA is just a moderate inhibitor of human alpha-thrombin (Ki = 0.18 microM) but a potent inhibitor of trypsin (Ki = 0.023 microM) and streptokinase (Ki = 0.035 microM). The relative lack of potency of CtA as a thrombin inhibitor is discussed with respect to certain structural features of the enzyme complex. We also report the total synthesis of CtA, by a convergent [2 + 3] fragment-condensation approach, to serve the preparation of cyclotheonamide analogues for structure-function studies.

Amino Acid Sequence↗
PubMed2000

Identification of the proximal ligand His-20 in heme oxygenase (Hmu O) from Corynebacterium diphtheriae. Oxidative cleavage of the heme macrocycle does not require the proximal histidine.

The coordination and spin-state of the Corynebacterium diphtheriae heme oxygenase (Hmu O) and the proximal Hmu O H20A mutant have been characterized by UV-visible and resonance Raman (RR) spectrophotometry. At neutral pH the ferric heme-Hmu O complex is a mixture of six-coordinate high spin and six-coordinate low spin species. Changes in the UV-visible and high frequency RR spectra are observed as a function of pH and temperature, with the six-coordinate high spin species being converted to six-coordinate low spin. The low frequency region of the ferrous RR spectrum identified the proximal ligand to the heme as a neutral imidazole with a Fe-His stretching mode at 222 cm(-1). The RR characterization of the heme-CO complex in wt-Hmu O confirms that the proximal imidazole is neither ionized or strongly hydrogen-bonded. Based on sequence identity with the mammalian enzymes the proximal ligand in HO-1 (His-25) and HO-2 (His-45) is conserved (His-20) in the bacterial enzyme. Site-specific mutagenesis identified His-20 as the proximal mutant based on electronic and resonance Raman spectrophotometric analysis. Titration of the heme-Hmu O complex with imidazole restored full catalytic activity to the enzyme, and the coordination of imidazole to the heme was confirmed by RR. However, in the absence of imidazole, the H20A Hmu O mutant was found to catalyze the initial alpha-meso-hydroxylation of the heme. The product of the aerobic reaction was determined to be ferrous verdoheme. Hydrolytic conversion of the verdoheme product to biliverdin concluded that oxidative cleavage of the porphyrin macrocycle was specific for the alpha-meso-carbon. The present data show that, in marked contrast to the human HO-1, the proximal ligand is not essential for the initial alpha-meso-hydroxylation of heme in the C. diphtheriae heme oxygenase-catalyzed reaction.

Bacterial Proteins↗
PubMed2000

Acyclic permutants of naturally occurring cyclic proteins. Characterization of cystine knot and beta-sheet formation in the macrocyclic polypeptide kalata B1.

Kalata B1 is a prototypic member of the unique cyclotide family of macrocyclic polypeptides in which the major structural features are a circular peptide backbone, a triple-stranded beta-sheet, and a cystine knot arrangement of three disulfide bonds. The cyclotides are the only naturally occurring family of circular proteins and have prompted us to explore the concept of acyclic permutation, i.e. opening the backbone of a cross-linked circular protein in topologically permuted ways. We have synthesized the complete suite of acyclic permutants of kalata B1 and examined the effect of acyclic permutation on structure and activity. Only two of six topologically distinct backbone loops are critical for folding into the native conformation, and these involve disruption of the embedded ring in the cystine knot. Surprisingly, it is possible to disrupt regions of the beta-sheet and still allow folding into native-like structure, provided the cystine knot is intact. Kalata B1 has mild hemolytic activity, but despite the overall structure of the native peptide being retained in all but two cases, none of the acyclic permutants displayed hemolytic activity. This loss of activity is not localized to one particular region and suggests that cyclization is critical for hemolytic activity.

Amino Acid Sequence↗
PubMed2002

(-)-Doliculide, a new macrocyclic depsipeptide enhancer of actin assembly.

The cytotoxic, cyclic depsipeptide (-)-doliculide was originally isolated by Ishiwata et al. (Ishiwata, H., Nemoto, T., Ojika, M., and Yamada, K. (1994) J. Org. Chem. 59, 4710-4711 and Ishiwata, H., Sone, H., Kigoshi, H., and Yamada, K. (1994) J. Org. Chem. 59, 4712-4713) from the sea hare Dolabella auricularia collected in Japanese waters, but the mechanism of action of the depsipeptide was not known. Using synthetic (-)-doliculide, we found that the compound arrests cells at the G(2)/M phase of the cell cycle by interfering with normal actin assembly. In cells, normal stress fibers disappeared and were replaced by multiple clumps of apparently aggregated F-actin. These effects of (-)-doliculide on cells were essentially identical to those obtained with jasplakinolide. Like jasplakinolide, (-)-doliculide caused the hyperassembly of purified actin into F-actin as measured both fluorometrically and by centrifugation. In addition, (-)-doliculide, like jasplakinolide, readily displaced a fluorescent phalloidin derivative from actin polymer. In these biochemical assays (-)-doliculide and jasplakinolide were quantitatively virtually identical in their behaviors. Similar effects have also been reported with a series of depsipeptides known as chondramides. Using recently developed, computer-driven shape descriptor analysis (Mansfield, M. L., Covell, D. G., and Jernigan, R. L. (2002) J. Chem. Inf. Comput. Sci. 42, 259-273), we compared (-)-doliculide with jasplakinolide, phalloidin, and chondramide C to gain insight into a possible pharmacophore that would explain the apparent binding of this diverse group of molecules at the same site on F-actin. We found that the segment of (-)-doliculide that best overlapped the other molecules encompassed its phenyl and isopropyl side chains and the portion of the macrocycle between these substituents.

Actins↗
PubMed2001

Resistance to macrocyclic lactone anthelmintics by Haemonchus contortus and Ostertagia circumcincta in sheep in New Zealand.

AIM: To establish the efficacy of oral formulations of ivermectin and moxidectin against naturally acquired abomasal nematode infections on a North Island sheep farm. METHODS: Two controlled slaughter trials were undertaken. In the first, 30 sheep on pasture were randomly allocated on the basis of faecal egg count to 1 of 3 groups, comprising an untreated control group and 2 treatment groups. One treatment group was given a single oral dose of ivermectin and the other a single oral dose of moxidectin, both at the manufacturer's recommended dose rates of 0.2 mg/kg liveweight. Six days after treatment, all animals were slaughtered and their abomasa recovered for worm counting. The second trial, which involved 47 animals, was essentially the same as the first except that, as well as involving the slaughter of 30 sheep from all 3 groups, 6 days after treatment, it also included a further 8 untreated control animals and 9 moxidectin treated animals which were slaughtered 27 days after treatment. RESULTS: At 6 days after treatment, moxidectin was highly effective against all 3 of the abomasal nematodes present. While ivermectin was similarly effective against Trichostrongylus axei 6 days after treatment, it was not effective against either Ostertagia circumcinta or Haemonchus contortus, against which average efficacies of only 63.6% and 61.6%, respectively, were recorded. At 27 days after treatment, moxidectin, was also highly effective against T. axei (97.3% reduction) but not against either H. contortus (71.4% reduction) or O. circumcinta (61.0% reduction). CONCLUSIONS: These results provide the first record of macrocyclic lactone resistance in H. contortus in sheep or in any other host in New Zealand, and the first case where such resistance has been exhibited in more than one parasite species at a time. Although the therapeutic efficacy of moxidectin was high against these resistant H. contortus and O. circumcincta strains, resistance to moxidectin was indicated by its diminished prophylactic activity against them. It is suggested that this reduction in the prophylactic activity of moxidectin is also likely to reduce its apparent current high therapeutic efficacy. CLINICAL RELEVANCE: As well as providing further evidence that it can no longer be automatically assumed that macrocylic lactone anthelmintics will be effective on sheep farms in this country, these findings also present a warning that increasingly complex parasite control options may have to be faced in the future.

Journal Article↗
PubMed2005

A survey of the prevalence of emerging macrocyclic lactone resistance and of benzimidazole resistance in sheep nematodes in the lower North Island of New Zealand.

AIM: To investigate the occurrence of emerging macrocyclic lactone (ML) resistance and of resistance to benzimidazole anthelmintics on a number of sheep farms in the North Island of New Zealand. METHODS: On commercial sheep farms (n=30) in the Taihape district in the North Island of New Zealand, 30 animals were randomly allocated to one of two equal-sized groups and treated with either half of the recommended dose rate of ivermectin (half of 0.2 mg/kg), or with the full recommended dose rate of oxfendazole (4.5 mg/kg). The ivermectin treatment only was used on a further six properties. Faecal egg counts, accompanied by pooled larval cultures, were conducted on all samples at the time of treatment and 7-10 days later. RESULTS: Resistance, as indicated by a <95% faecal egg count reduction (FECR) in both instances, was found to oxfendazole on 13/30 (43%) farms and to a half dose of ivermectin on 12/36 (33%) properties. For oxfendazole, such resistance was found to involve all six nematode genera whereas for ivermectin it was almost entirely restricted to Ostertagia and Cooperia infections. CONCLUSIONS: These results indicate that emerging ML resistance may be more common on sheep farms in New Zealand than is generally realised. They also suggest that the half-dose ivermectin faecal egg count reduction test (FECRT) may offer some very practical benefits for parasite control by providing early warning of developing resistance to ML drenches and by signalling the possible imminent failure of these at their therapeutic dose rates. The sensitivity and reliability of this procedure may be further enhanced by the inclusion of larval cultures.

Administration, Oral↗
PubMed2006

Farm management practices associated with macrocyclic lactone resistance on sheep farms in New Zealand.

AIM: To identify farm practices associated with the presence of resistance to a macrocyclic lactone (ML) anthelmintic on sheep farms in New Zealand. METHODS: A cross-sectional study was conducted to test for associations between the presence of resistance to an ML anthelmintic (ivermectin) and management practices on sheep farms in New Zealand. Selection of farms was both random (n=80) and purposive (n=32; being farms with a history of suspected ML resistance). Resistance was inferred from faecal nematode egg count (FEC) reduction (FECR) tests (FECRTs) when there was <95% reduction in FEC 7-10 days after treatment with a half dose of ivermectin (0.1 mg/kg). A logistic regression model was built to identify farm-level factors that were associated with the presence or absence of ML resistance. RESULTS: Of the 112 flock managers that were approached for interview, 103 (92%) returned useable questionnaires. The odds of ML resistance were increased: on farms that had used long-acting ML products in ewes as a pre-lambing treatment for > or =3 of the previous 5 years (odds ratio (OR) = 7.2; 95% confidence interval (CI) = 1.7-30.3); on farms where <70% of the total stock units mid-winter were from sheep (OR=6.5; 95% CI=1.6-25.6); on farms which over the year purchased >10% of the number of sheep present mid-winter (OR=7.1; 95% CI=1.5-34.7); and on farms where the average wool diameter of the main flock was <37 (OR=4.1; 95% CI=1.1-14.7) microns. The model provided a good fit to the data (pseudo R2=0.64; Hosmer-Lemeshow statistic = 0.38). CONCLUSIONS: Explanatory factors identified as associated with the presence of ML (ivermectin) resistance on farms included the use of long-acting anthelmintic formulations in ewes pre-lambing, sources of refugia of unselected parasites on the farm, breed of sheep and their requirements for anthelmintic treatments, and the importing of resistant parasites with purchased stock. The study provides support for controls that aim to provide refugia of susceptible worms and that minimise the risk of introduction of resistance through effective quarantine drenching.

Animal Husbandry↗
PubMed2006

Evidence that moxidectin is a greater risk factor than ivermectin in the development of resistance to macrocyclic lactones by Ostertagia spp in sheep in south eastern Australia.

AIM: To determine associations between resistance of Ostertagia (=Teladorsagia) spp to macrocyclic lactone (ML) anthelmintics and history of use of anthelmintics, by type, on commercial sheep farms in temperate regions of southern South Australia and Victoria, Australia. METHODS: Faecal egg count reduction tests (FECRTs) were conducted during a 2.5-year period (from August 2001 to January 2004) and records of the type of anthelmintic used in the 5 years preceding the FECRTs were collected from commercial sheep farms (n=103) in southern South Australia and Victoria, and data analysed retrospectively. ML resistance was defined as <95% reduction of Ostertagia spp 10-14 days after treatment with ivermectin (IVM), orally, at half the manufacturer's recommended dose rate. Use of anthelmintics in the preceding 5 and 10 years on each property was classified according to the nett number of years each of the following classes of drug had been used: IVM oral liquid (IVO), IVM controlled-release capsules (CRCs), abamectin (ABA), moxidectin (MOX) or a non-ML anthelmintic. The prevalence of ML resistance, by property, was analysed for associations with prior use of anthelmintics. RESULTS: Resistance by Ostertagia spp to ML anthelmintics was evident on 51/103 (49.5%) properties. The prevalence of resistance was lowest (23%) on properties on which MOX had not been used, and was significantly higher (64-77%) on properties on which MOX had been used for > or =2 of the preceding 5 years (p<0.001). In contrast, the prevalence of resistance was highest (70-74%) on the properties on which IVM, or IVM and/ or ABA, had not been used in the previous 5 years (on which the use of MOX was predominant), and was markedly lower (20- 42%) on properties that had used IVM or IVM and/or ABA for at least one of the preceding 5 years. Prevalence of resistance was higher for properties on which the only ML anthelmintic used was MOX (19/29=66%) than for those on which the only ML used was IVO (2/19=11%; p<0.001). Properties on which the only ML used was MOX were 2.72 times more likely to have resistance than properties on which the only ML used was IVO (95% confidence interval (CI) = 1.01-5.08). CONCLUSION: Use of MOX for > or =2 of the preceding 5 years was associated with a higher prevalence of resistance to ML by Ostertagia spp on sheep farms in south eastern Australia than the use of IVO.

Administration, Oral↗
PubMed2002

Cytotoxic macrocyclic trichothecenes from the mycelia of Calcarisporium arbuscula Preuss.

A new cytotoxic macrocyclic trichothecene calcarisporin B1 (1), and two known compounds roridin H (2) and roridin J (3) were isolated from the cultured mycelia of Calcarisporium arbuscula Preuss. The structure of 1 was determined to be 8alpha-acetoxy roridin H on the basis of spectral data. The cytotoxic activities of 1-3 were evaluated in vitro.

Ascomycota↗
PubMed2006

Elucidation of chiral recognition processes of macrocyclic antibiotic vancomycin.

A theoretical investigation was carried out on the retention and separation of enantiomeric molecules including nonsteroidal anti-inflammatory drugs, anti-neoplastic compounds and N-derivatized amino acids by capillary electrophoresis using macrocyclic antibiotics, a new class of chiral selectors, as stationary phase. Firstly docking methods were used to study the enantiorecognition in chiral electrophoresis. The molecular dynamics simulations of the two diastereoisomer complexes were then performed in order to understand how these antibiotics recognize the enantiomers. Another approach was applied in this study to establish a quantitative structure-enantioselectivity relationship (QSER) model, able to describe the resolution of a series of chiral compounds in capillary electrophoresis using vancomycin as the resolving agent.

Anti-Bacterial Agents↗
PubMed1993

In vitro DNA damage and mutations induced by a macrocyclic tetraamide chromium(V) complex: implications for the role of Cr(V) peptide complexes in chromium-induced cancers.

Electron paramagnetic resonance and electronic absorption spectroscopies have shown that unlike the bidentate Cr(V) complex [Cr(ehba)2O]- (ehba = 2-hydroxy-2-ethylbutanoato(2-)), I, the macrocyclic tetradentate complex, [Cr (mampa-dcb)(O)]- (mampa-dcb = 5,6-(4,5-dichlorobenzo)-3,8,11,13-tetraoxo-2,2,9,9-tetrameth yl-12,12-diethyl-1, 4,7,10-tetraazacyclotridecane), II, is substitutionally inert. Low levels of DNA strand cleavage were observed after treatment with II under physiological conditions (50 mM sodium phosphate, pH 7.4, 37 degrees C) at concentrations as high as 2 mM for periods as long as 2 days. II also induces a lower number of revertants in mutation assays with Salmonella typhimurium TA100 than I when identical Cr concentrations are applied. The slopes of the linear portion of the dose-response curves are parallel, however, indicating that the mutagenicity of II is comparable to I. II is stable toward ligand exchange, reduction and disproportionation in the mutagenicity test medium and also in the presence of bacteria and the common cell reductant, glutathione. This indicates that ligand exchange with DNA and/or reduction to Cr(IV) are not responsible for the mutagenicity of II (unlike I). It is believed that II reversibly but weakly intercalates with DNA placing the Cr(V) center in close proximity for hydrogen atom abstraction or oxo-transfer reactions to ensure. This tetraamide complex is a good structural and biomimetic model for non-sulfur-containing Cr(V) peptide species that may form in vivo from reactions of Cr(VI) with peptides. Hence, it is likely to be relevant to understanding one possible mechanism by which Cr(VI) causes cancer.

Chromium↗
PubMed1996

Evaluation of gadolinium 2,5-BPA-DO3A, a new macrocyclic hepatobiliary chelate, in normal liver and metastatic disease on high field magnetic resonance imaging.

RATIONALE AND OBJECTIVES: A new hepatobiliary gadolinium chelate, gadolinium (Gd) 2,5-BPA-DO3A, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved extracellular contrast agent, and Gd Cy2-DOTA, a second hepatobiliary chelate in preclinical development. The ligand in Gd 2,5-BPA-DO3A is macrocyclic in nature, as opposed to the linear structure of Gd DTPA. Gadolinium 2,5-BPA-DO3A was evaluated on magnetic resonance imaging at 1.5 T, examining specifically liver parenchymal enhancement and lesion delineation, the latter in metastatic disease. METHODS: Gadolinium 2,5-BPA-DO3A was evaluated in five normal rhesus monkeys and four New Zealand White rabbits with implanted VX-2 liver tumors. These studies were compared with magnetic resonance exams in the same animals using Gd HP-DO3A and Gd Cy2-DOTA. A contrast dose of 0.1 mmol/kg intravenous was employed in each instance, with the sequence of administration (for the three agents) randomized and at least 72 hours between injections. Spin echo breathhold T1-weighted scans were obtained before and at multiple times after contrast administration. Postcontrast scans were acquired from 1 to 60 minutes after injection in the monkeys and from 1 to 240 minutes in the rabbits. RESULTS: Enhancement of normal liver parenchyma was markedly superior with Gd 2,5-BPA-DO3A compared with Gd HP-DO3A and Gd Cy2-DOTA in both monkeys and rabbits. At 2 and 60 minutes after contrast administration, the liver signal intensity in the monkey was 452 +/- 56 and 440 +/- 69 with Gd 2,5-BPA-DO3A compared with 295 +/- 34 and 256 +/- 38 with Gd HP-DO3A. The difference between agents was statistically significant at all postcontrast time points in the rhesus monkey. Excretion of contrast into the gall bladder was consistently observed after Gd 2,5-BPA-DO3A injection in both animal species. Maximum lesion conspicuity occurred in the rabbit at 45 minutes after Gd 2,5-BPA-DO3A administration. At 45 minutes postinjection, liver-lesion contrast was 0.60 +/- 0.15 with Gd 2,5-BPA-DO3A, 0.35 +/- 0.11 with Gd Cy2-DOTA, and 0.12 +/- 0.04 with Gd HP-DO3A, with the differences between agents being statistically significant. CONCLUSIONS: Gadolinium 2,5-BPA-DO3A is superior to both Gd Cy2-DOTA and Gd HP-DO3A in the degree of enhancement of normal liver parenchyma achieved after intravenous injection. This leads to improved liver lesion delineation with Gd 2,5-BPA-DO3A on delayed postcontrast magnetic resonance scans.

Animals↗
PubMed2000

Synthesis, characterization, and imaging performance of a new class of macrocyclic hepatobiliary MR contrast agents.

RATIONALE AND OBJECTIVES: To investigate the effect of substituent lipophilicity, substituent position, and overall charge on the hepatobiliary clearance and tolerance of a series of aromatic ring-containing macrocyclic Gd chelates to select a candidate compound for evaluation as a hepatobiliary imaging agent. METHODS: Hepatobiliary clearance was studied in rats. Tissue distribution and tolerance were studied in mice. Imaging was performed in cats, rabbits, and Rhesus monkeys using T1-weighted pulse sequences or T1-weighted breath-hold pulse sequences. RESULTS: All the compounds were excreted bimodally. Gd-2,5-BPA-DO3A (15d) was found to have the optimal combination of hepatobiliary clearance (47% in rats, 29% in mice) and tolerance (minimum lethal dose 5.0 mmol/kg). Initial imaging studies in cats demonstrated the feasibility of Gd-2,5-BPA-DO3A for hepatic imaging. In rabbits with implanted VX-2 adenocarcinoma as a model for metastatic liver disease, Gd-2,5-BPA-DO3A provided sustained hepatic signal intensity (SI) enhancement and lesion conspicuity over a 120-minute imaging time course. In Rhesus monkeys with normal liver function, Gd-2,5-BPA-DO3A afforded sustained hepatic SI enhancement and a time-dependent increase in gallbladder SI over the entire 90-minute imaging time course. CONCLUSIONS: Gd-2,5-BPA-DO3A provides dramatic and sustained SI enhancement of hepatic tissue in cats, rabbits, and Rhesus monkeys that was superior in all respects to the extracellular space MRI agent, Gd-HP-DO3A, that was employed as a control.

Animals↗