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The utility of clinical magnetic resonance contrast media (MRCM) in the evaluation of pathologies within the central nervous system (CNS) is well established (1-9). Bloodbrain-barrier (BBB) disruption in tumors and other lesions of the CNS is attributable to abnormal endothelial junctions, and is a key feature of the aggressive neovascular formations within malignant tumors. This characteristic of BBB disruption accounts for the increased enhancement of intracranial tumors on MRI after administration of MRCM, which is helpful in delineating tumor anatomy. For gliomas, increased enhancement is suggestive, although not absolutely indicative, of an increased histological grade of malignancy. Degrees of tumor malignancy previously have been assessed in animal models using covalently Gd-conjugated macromolecule-based MRCM as MRI signal enhancers (3-6). However, these covalently-bound Gd-macromolecules have not been studied in clinical trials in humans. Hence, the available low-molecular-weight extracellular MRCM are now exploited under dynamic protocols for tumor assessment (7-9). These agents extravasate into extracellular space throughout non-CNS tissues, and thus present a limited time window at high concentration for the detection of CNS tumors. Despite successes achieved with the extracellular agents to date, the need for intravascular agents that would extravasate only in the face of BBB disruption continues to be advocated as a next step in improving the diagnostic utility of these and related techniques (10,11).Noncovalent albumin-binding Gd-chelates represent a new class of agents. These agents, unlike the covalently bound Gd-macromolecules, are small chelates with side chains that undergo reversible noncovalent interactions with circulating albumin (12,13). The bound form (the dominant species, with a Ͼ10-fold signal-enhancing potential) assumes the macromolecular attributes of albumin and remains intravascular, while the nonbound minor component (with the low relaxivity typical of small Gdchelates) is free and extravasates. MP-2269 (Mallinckrodt, Inc., St. Louis, MO) is an experimental monomeric Gd-DTPA-derived blood pool agent with a molecular weight of 1179 g/mol. It is the Gd complex of 4-pentylbicyclo-

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Although both MP-2269 and gadophrin-2 feature an albumin-binding capacity, only gadophrin-2 displayed a persistent necrosis-specific contrast enhancement in the rat model of reperfused liver infarction. Therefore, the role of albumin binding in the mechanisms of NACAs should be reevaluated.

A study including variable‐temperature and ‐pressure, multiple‐field 17O NMR, EPR and NMRD has been performed on the MRI contrast agent, [Gd(DTPA‐BMEA)(H2O)]. The water exchange rate [kex298 = (0.39 ± 0.02) × 106 s−1] and the activation volume (ΔV≠ = +7.4 ± 0.4 cm3 mol−1), hence the mechanism, are identical to those for [Gd(DTPA‐BMA)(H2O)]. The longer rotational correlation time of [Gd(DTPA‐BMEA)(H2O)], as obtained from a global analysis of 17O‐NMR, EPR and NMRD data, and compared to that of [Gd(DTPA‐BMA)(H2O)], can be explained by water molecules hydrogen‐bonded to the ether oxygen atoms of the ligand side chain.