Gd-EOB-DTPA

Liver Gadolinium EOB DTPA Primovist MRI product, not approved for CT phase I, II clinical trials Uptake into hepatocytes Schmitz SA et al (1997) Detection of focal liver lesions CT of the hepatobiliary system with gadoxetic acid disodium, or Gd-EOB-DTPA. Radiology 2002 399-405... 

Reimer P, Rmnmeny EJ, Shamsi K, Balzer T, Daldrup HE, Tombach B, Hesse T, Berns T (1996) Phase 11 clinical evaluation of Gd-EOB-DTPA dose, safety aspects, and pulse sequence. Radiology 199 177... 

The complex-forming ligands listed in Scheme 1 and also their Gd3+ complexes are generally hydrophilic. The exceptions are those ligands and complexes which possess lipophilic groups (e.g Gd(EOB-DTPA)2- [9, 10], Gd(BOPTA)2-... 

Several chelates have been developed to exploit the RIME approach. These include [Gd(B0PTA)(H20)]2 (Multihance , Bracco) [39], [Gd(EOB-DTPA)-... 

Fig. 9. The NMRD profile of the bound and the unbound populations of Gd(EOB-DTPA) in 4% HSA scaled to 1 mM [50]...

While differences in substituents on a core chelate may seem modest, the effects on protein binding can be very large. For example, MS-325 is reported to be 96.2% protein bound in human plasma at the clinical concentration of 0.1 mmole/L, and 94.3% bound in a 4.5% solution of HSA [46]. In contrast, Gd(EOB-DTPA) is only 10% bound in human plasma at a concentration of 1 mmole/L [40], and 11% bound in a 5% HSA solution with a Gd(EOB-DTPA) concentration of 1.5 mmol/L [50]. Thus, relatively modest changes in chelate structure can have large effects on protein binding, providing a route for fine tuning the MIME interaction for different applications. 

Fig. 11. Profiles taken at 10 MHz of 2-dimensional NMRD data sets, showing the distribution of proton T, values in a packed rat hepatocyte cell preparation with different concentrations of Gd(EOB-DTPA)...

The degree of biliary excretion is species dependent. Generally, mice, rats, and dogs have a better biliary excretion than rabbits, monkeys, and humans [118]. Gd-BOPTA has a 0.6 % biliary excretion in humans, the remainder being excreted in urine [119]. Gd-EOB-DTPA has a biliary excretion of 43.1-53.2%, a renal excretion of 41.6-51.2%, and an extrahepatic recirculation of about 4% in humans [120]. In various animals, excretion is slightly different. For example, the biliary excretion of Gd-BOPTA in rats is 55% and in rabbits is 25% [121], Gd-EOB-DTPA has a 63-80% biliary excretion in rats and a 32-34% excretion in monkeys [122]. 

Dohr, O., Hofmeister, R., Treher, M., and Schweinfurth, H. (2007) Preclinical safety evaluation of Gd-EOB-DTPA (Primovist). Investigative Radiology, 42, 830-841. 

Hamm, B., Staks, T., Miihler, A., et al. (1995) Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent safety, pharmacokinetics, and MR imaging. Radiology, 195, 785-792. 

Schuhmann-Giampieri, G, Schmitt-Willich, H., Press, W.R., etal. (1992) PrecUnical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system. Radiology, 183, 59-64. 

Narita M, Hatano E, Arizono S, Miyagawa-Hayashino A, Isoda H, Kitamura K, Taura K, Yasuchika K, Nitta T, Ikai I, Uemoto S (2009) Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma. J Gastroenterol 44 793-798... 

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