Sitharaman and wilson CAs used in clinical MRI procedures operate by changing the proton nuclear spin relaxation times of water molecules in their vicinity, enhancing the detected MR signal in tissue (Lauffer 1987; Caravan et al 1999; Merbach et al 2001; Krause and Editors 2002). Thus, the most commonly used clinical CAs decrease T1 relaxation times (also referred to as spin-lattice relaxation ) of water protons in living tissue in the vicinity of the paramagnetic CA. All CAs are paramagnetic (with unpaired electrons) because paramagnetic CAs generate very large lattice fields (magnetic and nuclear environments with which the protons interact during T1 relaxation) in the immediate neighborhood of the CA, which greatly shorten the T1 of any water molecule that approaches the paramagnetic center. The term “relaxivity” (r1 for T1 relaxation) is the key determinant for evaluating the efficacy of any MRI CA. It is defined as the change in the relaxation rate of the water protons per molar concentration of the paramagnetic CA, and is expressed in units of mM–1 sec–1. The high-spin paramagnetic gadolinium (Gd3+) metal ion is the most effective T1 relaxation agent. It has seven unpaired f-electrons, the greatest number of unpaired electrons exhibited by any atom or ion, a large magnetic moment (µ2=63µB2 where µB is the Bohr Magneton), and a highly symmetrical, slowly relaxing ground state (8S-state) which produces strong oscillations near the 1H Larmor frequency, and thus a strong T1 effect. The aquated Gd3+ ion is toxic, and therefore for medical use, its toxicity is usually sequestered by chelation with multidentate (linear and macrocyclic) ligands (Lauffer 1987; Caravan et al 1999; Merbach et al 2001). Despite the impressive progress in the design and synthesis of Gd3+ chelates for advanced CA applications, the resulting Gd3+ complexes still possess limitations. For example, magnetic resonance angiography (MRA or blood-pool imaging) requires long retention times in the circulatory system and almost all Gd3+ chelates are distributed extracellularly, with a low retention time in the blood pool (about 60 seconds), which makes them unsuitable for MRA. In addition, MRI of individual cells and their tissues (MR molecular imaging) requires that each Gd3+ center possess an extremely large relaxivity in order to induce sufficient signal intensity. This requirement is due to the fact that the concentration of Gd3+ centers that can be delivered or attached to the surface of a specific cell is largely limited to the nanomolar (nM) range by biological constraints (Nunn et al 1997). Gadolinium CAs in current clinical use with r1 ~4 mM–1 s–1 do not possess sufficiently large relaxivities for molecular imaging since r1 values greater than 100 mM–1 s–1 are generally required (Nunn et al 1997). 292 Gadonanotubes Gd3+-based carbon nanotube structures with their unique nanoscalar properties and superior performance as MRI CAs show promise for molecular imaging and other advanced applications. Single-walled carbon nanotubes (SWNTs) possess unique characteristics that make them desirable for biomedical applications (Martin and Kohli 2003). The ideal length for medical applications is uncertain, but ultra-short nanotubes (20–100 nm) or US-tubes (Gu et al 2002; Mackeyev et al 2005) are probably best suited for cellular uptake, biocompatibility, and eventual elimination from the body. Additionally, the US-tube exterior surface provides a versatile scaffold for attachment of chemical groups for solubilizing or targeting purposes, while its interior space allows for encapsulation of atoms, ions, and even small molecules (Suenaga et al 2000; Monthioux 2002; Mackeyev et al 2005) whose cytotoxicity may be sequestered within the short carbon nanotube. Finally, medical-imaging agents derived from US-tubes hold promise for intracellular imaging, since carbon nanotubes have been shown to translocate into the interior of cells with minimal cytotoxicity (Dugan et al 1997; Wang et al 1999; Kam et al 2004; Lu et al 2004; Pantarotto et al 2004). Recently, the first carbon nanotube-based CA called a “gadonanotube” (Figure 1 inset) was reported (Sitharaman et al 2005). This CA harnessed the ability of ultra-short single- walled carbon nanotubes (US-tubes) to encase smaller ions or molecules within their framework by successfully loading and confining aquated Gd3+n-ion clusters within the nanoscalar confines of the US-tubes. Relaxometry and magnetometry Figure 1 Nuclear magnetic relaxation dispersion profile measured for Gd3+n@ US-tubes in a 1% sodium dodecylbenzene sulfonate solution (cGd = 0.044 mM; T = 37°C ) (◆). For comparative purposes, data for the commercially available CA, MagnevistTM or (Gd[DTPA])2– (▲), are also shown. inset: Depiction of a single US-tube loaded with hydrated Gd3+ ions through sidewall defects created by cutting full-length nanotubes to produce US-tubes (not to scale and Cl– anions and atoms attached to dangling C bonds not shown). international Journal of Nanomedicine 2006:1(3)