## 3 Results and Discussion
In both cases shown, the infused agent  
Figure 5: Analysis by HPLC of the iodinated product \({}^{124}\)I-f-Gd\({}_{3}\)N(\(\circled{\rm C}_{80}\) (solid lines) showing detection by UV absorption (red trace—right axis) and radioactivity (black trace—left axis). The slight offset in the two traces is due to the detectors being connected in series. The trailing peak in the radioactive trace for the \({}^{124}\)I-f-Gd\({}_{3}\)N(\(\circled{\rm C}_{80}\) product was confirmed to be free \({}^{124}\)I as evidenced in the matching retention time for \({}^{124}\)I alone injection (dashed line—black trace). is located within the tumor. This is further evidenced by the \(\rm T_{2W}\) images in Figure 6(C,F) which show dark contrast (due to high \(\rm T_{2}\) relaxivity) at the infusion site in the center of the tumor outlined by bright contrasting peritumoral edema. Other rats infused identically to those above were subjected to microPET imaging; the resulting images from a representative rat are shown in Figure 6(G-L). Figure 6(J-L) was collected 2 h post \({}^{124}\)I-f-Gd\({}_{3}\)N@C\({}_{80}\) infusion by imaging for 5 min on the microPET scanner and illustrates the intratumoral distribution of the \({}^{124}\)I. The \({}^{18}\)F-FDG image obtained subsequently (Figure 6(G-I)) provides an anatomical reference for the location of the tumor and infusion site. These results show that the position of the infusion site seen in the microPET image is comparable with the positions evident in the MR images. These studies have produced a dual-modality agent through the combination of a nanoplatform based MR T1 agent with high relaxivity (Gd3N(\(\bar{\varrho}\)C80) and a \({}^{124}\)I label for PET detection. The use of \({}^{124}\)I is advantageous due to the facile and rapid radiolabeling process that yields a product having high radiochemical purity. In addition, relaxivity r1 values of 70 s\({}^{-1}\cdot\)mM\({}^{-1}\) with respect to Gd concentration have been reported for the carboxyl and hydroxyl functionalized Gd3N(\(\bar{\varrho}\)C80 (f-Gd3N(\(\bar{\varrho}\)C80), which is over an order of magnitude greater than most chelate-based contrast agents [34]. The high stability of the metallofullerene cage also provides a robust means for isolating the free metal from the biological system thus suppressing toxic side effects [46,47]. Although the stability of the iodinated form of the f-Gd3N(\(\bar{\varrho}\)C80 (\({}^{124}\)I-f-Gd3N(\(\bar{\varrho}\)C80) will require further investigation, our preliminary study suggested a negligible amount of free \({}^{124}\)I as indicated by a lack of thyroid uptake in the PET scans following infusion of the radio-iodinated agent. The _in vivo_ imaging investigations have clearly demonstrated the dual properties of the \({}^{124}\)I-f-Gd3N(\(\bar{\varrho}\)C80 agent through visualization in orthotopic T9 tumors with both MRI and microPET imaging with confirmation of anatomical location using subsequent \({}^{18}\)F-FDG microPET scanning. The use of CED in this study to deliver the agent directly into the tumor was chosen to bypass the blood brain barrier (BBB), in order to sufficiently demonstrate image acquisition orthotopically. Although CED administrations are currently used selectively in the clinic to deliver high doses of therapeutic agents directly into malignant tumors, ultimately it would be desirable to have these imaging agents administered intravenously as well. Surface modifications to metallofullerenes have been attempted to allow for limited opsonization and diffusion across the BBB (e.g., polyethylene glycols) [46]; however, further studies are needed to elucidate the most favorable surface coating. Additionally, the optimal use of the agent will be realized with investigations using integrated and simultaneous PET/MR scanners now under development and testing.