Water-Soluble Gadofullerenes:  Toward High-Relaxivity, pH-Responsive MRI Contrast Agents

Abstract

The water-soluble endohedral gadofullerene derivatives, Gd@C(60)(OH)(x) and Gd@C(60)[C(COOH)(2)](10), have been characterized with regard to their MRI contrast agent properties. Water-proton relaxivities have been measured in aqueous solution at variable temperature (278-335 K), and for the first time for gadofullerenes, relaxivities as a function of magnetic field (5 x 10(-4) to 9.4 T; NMRD profiles) are also reported. Both compounds show relaxivity maxima at high magnetic fields (30-60 MHz) with a maximum relaxivity of 10.4 mM(-1) s(-1) for Gd@C(60)[C(COOH)(2)](10) and 38.5 mM(-1) s(-1) for Gd@C(60)(OH)(x) at 299 K. Variable-temperature, transverse and longitudinal (17)O relaxation rates, and chemical shifts have been measured at three magnetic fields (B = 1.41, 4.7, and 9.4 T), and the results point exclusively to an outer sphere relaxation mechanism. The NMRD profiles have been analyzed in terms of slow rotational motion with a long rotational correlation time calculated to be tau(R)(298) = 2.6 ns. The proton exchange rate obtained for Gd@C(60)[C(COOH)(2)](10) is k(ex)(298) = 1.4 x 10(7) s(-1) which is consistent with the exchange rate previously determined for malonic acid. The proton relaxivities for both gadofullerene derivatives increase strongly with decreasing pH (pH: 3-12). This behavior results from a pH-dependent aggregation of Gd@C(60)(OH)(x) and Gd@C(60)[C(COOH)(2)](10), which has been characterized by dynamic light scattering measurements. The pH dependency of the proton relaxivities makes these gadofullerene derivatives prime candidates for pH-responsive MRI contrast agent applications.

The magnetic, relaxometric, and optical properties of gadolinium-catalyzed single walled carbon nanotubes

“…The difference between the experimental and theoretical J values could be due to transfer of electron spins onto the carbon nanotubes similar to a process postulated for gadofullerenes. 23 Further electron paramagnetic resonance (EPR) investigations are necessary to confirm this spin transfer, since trace organic impurities or carbon debris present in the sample could also be the cause of the difference in l eff . B. Relaxivity, nuclear magnetic dispersion profiles NMRD measurements provide valuable insights and information about the dynamic, and structural parameters of MRI CAs that influence relaxivity.…”

High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

“…[40][41][42] The peripheries of these cages are decorated with solubilizing groups to allow for application of C 60 in aqueous media. Relaxivities ranging from about 10 to as high as 38.5 mM -1 s -1 (30 MHz, 26 °C) are due entirely to second and outer-sphere relaxation, as there are no inner-sphere waters directly coordinated to the Gd.…”

“…In solution, these "gadofullerenes" aggregate, resulting in large assemblies with long rotational correlation times and consequent high relaxivities. [42] However, practical concerns such as in vivo toxicity and deaggregation in the presence of various salts (thereby limiting the effect of long τ R values on relaxivity) [43] may preclude considering such systems for contrast agent applications.…”

All a-Twitter about chemistry

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