DOTA

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SWNTs-[(DOTA) (AF488) (AF680)] HiPCO Mice... 

Figure 2 The molecular dynamics simulation picture of [Gd(DOTA)(H20)] in aqueous solution shows the inner sphere water, directly bound to the metal (its oxygen is dark) the second sphere water molecules, bound to the carboxylates of the ligand through hydrogen bridges (their oxygens are gray) and outer sphere or bulk water molecules without preferential orientation (in white).

Figure 4 Two diastereoisomeric isomers of DOTA-type Lnm complexes.

Figure 5 Typical NMRD curves of monomer Gdm complexes with one ([Gd(DOTA)(H20)] and [Gd(DTPA)(H20)]2 ) and with two inner-sphere water molecules ([Gd(HTTAHAXH20)2]2 ).

Complex stability constants are most often determined by pH-potentiometric titration of the ligand in the presence and absence of the metal ion.100 This method works well when equilibrium is reached rapidly (within a few minutes), which is usually the case for linear ligands. For macrocyclic compounds, such as DOTA and its derivatives, complex formation is very slow, especially for low pH values where the formation is not complete, therefore a batch method is... 

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... 

PAMAM dendrimers of different generations have been loaded with DOTA-type129,130 or DTPA-type131-133 chelates, most often using the p-NCS-benzyl linker. For these types of... 

Dextrans are also attractive as macromolecular carriers of paramagnetic chelates because of their hydrophilicity, the different available molecular weights with narrow polydispersity, and the versatility of activation methods applicable. Several DTPA- or DOTA-loaded carboxymethyl dextran (CMD) derivatives have been prepared and tested in blood pool MRI.136-139 The relaxivities reported for these compounds are, however, relatively moderate. 

The high in vivo stability of DOTA complexes makes it a desirable ligand framework for BFCAs relative to acyclic analogs however, complex formation with DOTA and its analogs can be slow. The slow kinetics of complex formation with DOTA-type ligands does not pose problems with nuclides such as 177Lu (t /2 6.64 d) however, improved reaction conditions may... 

There are several methods used to conjugate DOTA and other polyaminocarboxylate ligands to biomolecules.140,141 The simplest method, commonly used in solid-phase peptide synthesis, is the... 

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