Gd-DTPA

The Gd-H distance, /-GdH, which enters at the inverse sixth power into the expression of inner-sphere relaxivity, is a difficult parameter to obtain experimentally. It is generally estimated on the basis of Gd-coordinated water oxygen distances, determined by solid-state X-ray analysis. Solid-state distances are good estimates of the aqueous solution state, as was experimentally proven by an X-ray absorption fine-structure study on [Gd(D0TA)(H20)] and [Gd(DTPA)(H20)]2, which gave identical values for the Gd-0 distances for both complexes in solid and solution states.20... 

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 ).

In practice, some contrast agent formulations also include a small amount of the corresponding Ca11 chelate ( 5%) which acts as a sacrificial complex to pre-empt displacement of Gdm from GdL by adventitious Zn2+. As a result, the LD50 value for Gd(DTPA-BMA) increased from 14.8 mmol kg-1 to 38.2 mmol kg-1 upon addition of the adjuvant Ca11 complex.103... 

The competitive equilibria based on the different plasma models cannot solely explain the in vivo behaviour of Gd111 complexes. The excretion of low molecular weight Gd111 chelates from the body is very rapid (e.g., t1/2 = 1.6 h for [Gd(DTPA)]2 ),M0 whereas the dissociation and trans-metallation of the Gd111 complexes is relatively slow. Therefore, the system is far from equilibrium and kinetic factors could substantially change the predicted amount of free Gd3+. 

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... 

Gd(DTPA-bisamide)-PEG copolymers52 are also flexible, which explains their low relaxivity. A combined nO NMR, EPR, and NMRD study performed on [Gd(DTPA-BA)-PEG]x concluded that the effective rotational correlation time in the long polymer chain is not higher than that of the same Gd111 monomer unit, Gd(DTPA BMA) restricted to rotate around a single axis (tr for the polymer equals three times the rR for the monomer).52 An interesting feature of this... 

Figure 9 pH-sensitive paramagnetic liposomes at physiological pH and above, Gd(DTPA-BMA) is entrapped in the liposome and the relaxivity is low due to the low water exchange rate (/cex) through the liposome membrane. At lower pH, the liposome is disrupted and the relaxivity increases.172... 

Wiener and co-workers used folic acid-conjugated Gd(DTPA)-PAMAM dendrimers for visualizing the high-affinity folate receptor, overexpressed in many tumors.201 The contrast agent accumulated in the cells, resulting in a remarkable contrast enhancement on 7)-weighted images. 

Fig. 8 Nanosystems that may function as simultaneous drug delivery and imaging agents for targeting T cells (a) liposomal systems, (b) solid biodegradable nanoparticulates, and (c) macro-molecular dendrimer complexes. PEG polyethylene glycol, Gd-DTPA gadolininum-diethylene triamine penta acetic acid. (Adapted from [48])...

Fig. 10 Multifunctional solid biodegradable PLGA nanoparticles attached to several moieties such as T-cell antibodies, magnetic resonance contrast agent (biotin-BSA-Gd-DTPA) and encapsulated immunosuppressive drug (doxorubicin). (Adapted from [48])...

Annexin V-functionalized crosslinked iron oxide (CLIO) was designed as a contrast agent for MRI, which was additionally labeled with Cy5.5 to allow colocalization with optical imaging techniques [98]. Alternatively, conjugation of multiple Gd-DTPA molecules or SPIO particles to the C2 domain of synaptotagmin I was shown to allow the detection of apoptotic cells in vitro [99]. Zhao et al. [100] were the first to apply a C2 domain-functionalized SPIO and showed very promising results for future in vivo applications of MR contrast agents for the detection of apoptotic sites. 

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