Targeting of ultrasmall superparamagnetic iron oxide (USPIO) particles to tumor cells in Vivo by using transferrin receptor pathways

Human transferrin was covalently coupled to ultrasmall superparamagnetic iron oxide (USPIO) particles, and the trans‐ferrin‐USPIO obtained was investigated in vivo in experimental SMT/2A tumor‐bearing rats (rat mammary carcinoma). Physicochemical characterization showed an overall size of 36 nm (DLS) with a core size of 5 nm (TEM). Relaxivities were R,1 = 23.6 and R2 = 52.1 liter/mmol · s (0.47 T). Bound transferrin was 280 μg/mg of iron. Pharmacokinetic investigations revealed a half‐life of 17 min in normal rats. The MR evaluation of tumor signal intensity over time showed a 40% (range 25–55%) signal reduction 150 min after injection with the reduction persisting for at least 8 h. Control experiments using the parent USPIO compound or USPIO labeled with a nonspecific human serum albumin (HSA‐USPIO) showed a change of only 10% (range 5–15%) in tumor signal intensity over time. The results demonstrate that a combination of the USPIO relaxivity properties with the specificity of transferrin‐medi‐ated endocytosis allows in vivo detection of tumors by MR imaging.

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