Ferumoxytol has gained increasing attention as a negative MR-contrast agent due to its high r2* relaxivity [1]. Due to its specific uptake by the monocyte−macrophage system in the liver, spleen, bone marrow and lymph nodes, it is a promising agent to identify metastatic disease in these organs [2]. However, limited data are available regarding the temporal course of the biodistribution of ferumoxytol, which is necessary to determine the optimal imaging delay after administration, and to understand the long-term signal alterations in MRI after ferumoxytol administration [3,4,5]. The purpose of this study was to evaluate the biodistribution of ferumoxytol in different tissue types using repeated MR-measurements until the 30th day after ferumoxytol administration. Scanning was performed after IRB approval and informed written consent on a clinical 3T-MR system (MR750, GE Healthcare, Waukesha, WI). Subjects: 7 healthy volunteers were recruited for this study. Subjects were assigned to either 2mg/kg (n=3) or 4mg/kg (n=4) of ferumoxytol. Each of the subjects was scanned immediately before and 1, 2, 4, 7, and 30 days after injection. MRI protocol: The MRI protocol included R2*-mapping based on a chemical shift encoded (CSE) 3D- spoiled-gradient-echo with the following imaging parameters: TR=8.02ms, TE1=1.24ms, ΔTE=1.01ms, echoes=6, FOV=400x360x320mm, flip angle=4°, receiver bandwidth=±125kHz. R2* measurement: The CSE imaging data were processed using a confounder-corrected R2* mapping algorithm, and R2* was measured by drawing regions-of-interest (ROIs) in the following structures/organs: aorta, thoracic vertebral body, subcutaneous fat, inferior vena cava, kidney, liver, pancreas, spleen and spinal musculature. One of the subjects had iron overload and was therefore excluded from the study (assigned to 2mg/kg). Volunteers receiving 2mg/kg of ferumoxytol: R2* values are summarized in Table 1 (Fig.1). The highest R2* values in blood (aorta, inferior vena cava) were measured 1 day after injection and returned to baseline on day 4 after injection (no significant difference between baseline R2* and R2* at day 4 (p=0.22)). Temporal R2* changes of kidney, muscle and pancreas were similar to those of blood pool. The R2* of these tissues peaked 1 day after injection and returned to baseline on day 4 after injection (Fig. 1) without significant differences between baseline R2* values and the R2* at day 4 (kidney p=0.9, muscle p=0.9, pancreas p=0.6). Tissues of the monocyte−macrophage system (liver, spleen, bone marrow) peaked at day 1 (liver and spleen) or day 2 (bone marrow, Fig. 1) without significant differences between baseline R2* and the R2* on day 30 after injection (liver: p=0.2, spleen: p=0.52, bone marrow: p=0.38). Volunteers receiving 4mg/kg of ferumoxytol: R2* values are summarized in Table 1. The highest R2* values in blood (aorta, inferior vena cava) were measured 1 day after injection and returned to baseline on day 7 after injection without significant differences between baseline R2* and the R2* at day 7 (p=0.72). Temporal R2* changes of kidney, muscle and pancreas were similar to those of blood pool. The highest R2* values within these tissues were measured 1 day after injection and returned to baseline values on day 7 after injection (Fig. 2) without significant differences between baseline R2* and the R2* on day 7 (kidney p=0.16, muscle p=0.67, pancreas p=0.6). Tissues of the monocyte−macrophage system (liver, spleen, bone marrow) showed highest R2* values at days 1, 2, and 4 for liver, spleen and bone marrow respectively (Fig. 2). The R2*-values of these tissues showed a marked decrease, but remained above baseline levels on day 30 after injection with significant differences to baseline for liver (p=0.05) and bone marrow (p=0.007). The R2* in adipose tissue did not demonstrate any ferumoxytol related changes in either group (Fig. 1,2).In this longitudinal MRI-study of ferumoxytol biodistribution, tissues of the monocyte−macrophage system (liver, spleen, bone marrow) demonstrated maximum R2* changes at different time points. In contrast to administration of 2mg/kg, R2* values following administration of 4mg/kg remained significantly above baseline for liver and bone marrow at day 30, concordant with existing data [5]. Evaluated tissues not belonging to the monocyte−macrophage system showed R2* changes similar to blood. These tissues returned to baseline R2* values with a dose dependent time course that paralleled the blood pool. Tissues of the monocyte−macrophage system demonstrated different times to reach maximum R2* changes after ferumoxytol injection. Therefore, varying imaging time points may be optimal for different MR-applications. Tissues not containing monocytes/macrophages parallel the time course of ferumoxytol in the blood pool. Expectable long-term R2* changes after ferumoxytol differ significantly with dose and may last beyond 30 days after injection [5].