Sitharaman and wilson relaxivity is particularly important (Mansfield 2004) given the current tendency to develop MRI scanners of higher and higher fields; at these same fields, the contrast-enhancing effect of traditional CAs drops off. Currently, the most efficient T1 agents show a typical high-field relaxivity peak centered around 30–40 MHz which is characteristic of slow molecular rotation which can give maximum relaxivities of 40–50 Mm–1 s–1. Above this frequency, the relaxivity quickly vanishes to very small values for current MRI CAs. In this respect, gadonanotubes may represent a significant breakthrough in CA design for high-field imaging. Cellular- and molecular-imaging probes Molecular imaging is a new frontier for diagnostic medicine. It aims to strengthen diagnostic accuracy of existing image modalities and their interpretation by probing unique biological signatures or sub-cellular processes that are at the cause of disease. The gadonanotube materials considered here would seem to hold exceptional promise for molecular imaging for the following reasons: a) Their external surfaces can be used as a scaffold to attach a wide variety of agents. These agents can be water- solubilizing groups, biocompatible coverings, and even antibodies or peptides for active targeting of a specific cell type of interest, such as malignant cells. b) Biological constraints limit targeted receptor sites on cell surfaces to very low concentrations (nM–pM/g of tissue) (Nunn et al 1997). The exceptionally large T1 relaxivities of the gadonanotubes (Figure 1) could provide sufficient signal- to-noise to image cell-surface receptor sites in the nanomolar range. For example, for a clinical CA with r1= 4.0 mM–1 s–1 at clinical field strengths, the minimum detectable concentration of Gd3+ is 10–4M (Nunn et al 1997). The increase in relaxivity provided by the gadonanotube changes this minimum concentration to approximately 2 x 10–9 M. c) Recently, SWNTs 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). Thus, CA probes derived from these materials could also accumulate within targeted cells to further boost MRI signal strength. For example, we estimated that a (10 nm x 100 nm) gadonanotube probe, with r = 170 mM–1 s–1 per Gd3+ at clinical fields, contains about 100 1 Gd3+ ions. This should give an effective r1 = 17 000 mM–1 s–1 per probe. (Here we have estimated the T1 relaxation rate per nanoprobe, since the relaxation effect will be due to the entire densely-packed nanoprobe rather than individual Gd centers.) If just 1000 such probes were to accumulate within a single 294 cell, the relaxivity of the cell would be 17 000 000 mM–1 s–1 (!) which should easily permit cellular imaging. The use of progenitor and stem cells in humans for cellular therapies will require a technique that can accurately monitor their fate and delivery noninvasively and repeatedly. MRI is ideally suited to study the migration and tissue integration of magnetically labeled adult stem cells. Early detection of cancer cells would be another very desirable application of such a intracellular molecular-imaging capability. Guided-therapy probes The superparamagnetic gadonanotubes also show promise for the development of the first Gd3+-based MRI image-guided therapeutic agent that can used for targeted magnetic-field- induced hyperthermia. While heating a cancer cell or tumor to the point of therapeutic destruction can be accomplished by several methods (Moroz et al 2002), the least intrusive is the use of a magnetically mediated agent. Although any magnetic material can be magnetically induced to generate heat, single domain particles (superparamagnetic materials like the gadonanotubes) are preferred because they can produce far more heat at safer (lower) magnetic fields compared with ferromagnetic materials (Moroz et al 2002). The limitation of hyperthermia for human treatment is the failure to generate appreciable heat at safe magnetic fields. However, recent results with ultra-small iron oxide particles (USPIOs) have shown promise for the first human trials (Moroz et al 2002). The gadonanotubes may make ideal MRI-delivery capsules for cancer imaging–therapy by magnetic hyperthermia due to their nanoscalar size, superparamagnetism, external derivatization potential, and intrinsically intracellular nature. Furthermore, non-spherical particles such as the gadonanotubes are yet to tested as hyperthermia agents, and it is possible that their unique rod-shaped geometry (aspect ratio of 100:1) may augment performance through non-axial Brownian relaxation (Rosensweig 2002). Acknowledgment The original research reviewed and discussed in this chapter was supported by the NIH (Grant 1-R01-EB000703) and the Robert A Welch Foundation (Grant C-0627). We thank Professor Andre Merbach’s group at the Ecole Polytechnique Fédérale de Lausanne, EPFL-BCH; CH-1015 Lausanne, Switzerland for the NMRD data as well as Dr Raja Muthupillai and Dr Scott D Flamm for the MRI phantom imaging. SB acknowledges support by the J. Evans Attwell- Welch postdoctoral training fellowship. international Journal of Nanomedicine 2006:1(3)