Macromolecular Agents

Aime et have prepared and characterized adducts of Gd complexes to cyclodextrin. 

1 Micellar Contrast Agents. One strategy for increasing reorientational correlation time is to incorporate the Gd complex into a micelle. Kimpe et have 

Morales et al. report the synthesis and proton relaxivity of colloidal dextran-coated Fe-O nanoparticles approximately 50 nm in diameter with a unimodal size distribution. Kim et a/. report the synthesis and relaxation properties of starch-coated Fe-O nanoparticles 6 nm in diameter. 

4 Dendrimeric Contrast Agents. A review has been prepared by Kobayashi and BrechbieF In recent work, Wang et al. report the Ti field dispersion profiles of a new Gd(III) contrast agent prepared from polypropyleneimine dendrimers, generation 2. Yordanov et al. have used Gd(III) dendrimers as biometric nanoprobes to detect vascular permeability. Francese et al. have characterized proton relaxivity of PAMAM dendrimers functionalized by nit-ronyl nitroxide radicals. 

Maliakal et aV have studied the proton relaxivity produced by dinitroxide spin labels attached to poly(propylene imine) dendrimers as potential MRI contrast agents. They find that proton relaxivity, which is substantially higher than for mononitroxide spin labels, is not seriously affected by electron selfexchange. 

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This method represents one of the first attempts towards macromolecular agents.121-123 As many as 60-90 [Gd(DTPA)]2- or [Gd(DOTA)] chelates were first linked to a polylysine chain, then covalently conjugated to a HSA molecule.124 The increase in relaxivity per Gd, as compared with the monomeric chelate, was remarkable (two- to threefold), though far from optimal. However, the development of these albumin conjugates was abandoned at an early stage, since their synthesis is not easily controlled, and there are also toxicity concerns due to the retention of gadolinium observed in the bones and liver.125... 

For monomer Gd(III) complexes the inner and outer sphere mechanisms contribute more or less to the same extent to the overall paramagnetic relaxation enhancement. The development of high relaxivity contrast agents mainly involves increasing the inner sphere term, since the outer sphere contribution can hardly be modified. For the new generation macromolecular agents, therefore, the inner sphere relaxivity becomes much more significant (over 90% of total relaxivity). 

The flexibility of the linker group was found to be responsible for the much lower effective rotational correlation time, consequently lower relaxivity of many different types of macromolecular agents. For dendrimers loaded with... 

Most effective delivery of the macromolecular agent through the BBB is achieved when the agent is injected, simultaneously, with the microbubbles, while exposing the target volume to the ultrasound (9). The macromolecular agent can be injected after the sonications and, at least for smaller molecules, some BBB penetration will remain up to approximately 6 h after the exposure. 

Since granulocytes prepared by centrifugation are markedly contaminated with erythrocytes, the ABO compatibility between donor and recipient will be important unless the erythrocytes can be removed before use. Some reactions, particularly allergic and febrile complications, are associated with the presence of macromolecular agents (hydroxyethyl starch, modified gelatin, dextran), used to increase the yield of centrifugal techniques. ABO incompatibility does not alter the in vivo fate of granulocytes (39). 

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