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 superparamagnet ic iron oxide (USPIO) particles, and the transferrin-USPIO obtained wa s 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 R-2 = 52.1 liter/mmol . s (0.47 T). Bound transferrin was 280 mu g/mg of iron. Pharmacokinetic investigations revealed a hal f-life of 17 min in normal rats. The MR evaluation of tumor signal int ensity over time showed a 40% (range 25-55%) signal reduction 150 min after injection with the reduction persisting for at least 8 h, Contro l 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 demon strate that a combination of the USPIO relaxivity properties with the specificity of transferrin-mediated endocytosis allows in vivo detecti on of tumors by MR imaging.