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R S Ranganathan

Publications and source records attributed to R S Ranganathan.

8 recordsLinked to original sources
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.

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PubMed1998

New multimeric magnetic resonance imaging agents.

RATIONALE AND OBJECTIVES: The authors investigated the effect of multimerization on the relaxivity of macrocyclic gadolinium (Gd) chelates. The objective was to develop more sensitive magnetic resonance imaging (MRI) contrast agents to study biochemical processes. METHODS: Covalently linked nonionic, macrocyclic, multimeric lanthanide chelates that belong to the classes of dimers, trimers, tetramers, hexamer, and octamer, in the molecular weight range approximately 1 to 5 KDa, were synthesized. The chemical linkage was based on either the amide bond or the 2-hydroxypropylidene bond. Relaxivity values, 20r1, on Gd3+ chelates and hydration numbers, Q, on Tb3+ chelates were determined. RESULTS: Relaxivity values increased with molecular weight and Q values were not affected, the increase in r1 in attributable to the expected increase in the overall rotational correlation time, tau r with an increase in molecular weight. The rigidity of the linkers, which is expected to affect the intrachelate rotational correlation time tau r* that makes a contribution to the overall correlation time, tau r, exerted a noticeable effect. The hydroxyl-based chelates generally had lower r1 values than the amide-based chelates. This is rationalized as arising from the longer and thereby rate-limiting effect of the tau m value for the hydroxyl chelates compared with that reported of the amide-based chelates. This rate limiting effect of tau m becomes a dominant factor controlling attainable enhanced relaxivity when multimers based on traditional chelate designs are used for MRI applications. CONCLUSIONS: Approaches aimed at enhancing relaxivity by modulating the water relaxation time, tau m, will be important for the future development of functional MRI contrast agents for the imaging of biochemical processes.

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PubMedDate not supplied

Iotrol, a new myelographic agent: 1. Radiography, CT, CSF clearance, and brain penetration.

Four new myelographic agents, metrizamide, iopamidol, iohexol, and iotrol, were studied in the subarachnoid space of cynomolgus monkeys. Plain films and computed tomographic scans documented the transport of each material throughout the space and into the brain. At the concentration used (300 mg I/ml), all gave good radiopacity for myelography and delineation of the cerebral subarachnoid space. All four cleared similarly from the ventricular system. Metrizamide, however, penetrated the brain in greater degree and persisted longer than the other three agents. Next in persistence was iopamidol and least, and both statistically equal, iotrol and iohexol.

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