Abstract: The folate receptor is a useful target that has been exploited for tumor-specific drug delivery. In this study, Human serum albumin-folate conjugate(HSA-FA) was prepared with HSA as the linker and drug carrier. Coupling degree of the conjugate show that one molecule of HSA is loaded with about three folic acid molecules. The corresponding 99mTc-complex was successfully obtained by SnCl2·2H2O as reducing agent. The radiochemical purity of the product was above 90% by TLC and HPLC. The results of in vitro experiments show that the complex bound the KB tumor cells specifically. In vivo study of 99mTc-HSA-FA was performed in Kunming mice bearing S180 tumor. Compared with 99mTc-HSA, the biodistribution of 99mTc-HSA-FA was different and the tumor uptake was significantly increased(t=12.03, P<0.05). 99mTc-HSA-FA showed a high accumulation[(4.37±1.12)%ID/g at 1h] and good retention[(3.40±0.69)%ID/g at 4 h] in tumor. The ratios of tumor/blood and tumor/muscle increased with time and were 0.45 and 4.28 at 1 h post injection, and reached 0.76 and 5.00 at 4 h post injection, respectively. After blocking with the cold ligand, the uptakes of kidney and tumor were lower than the control(t=24.17 and 17.87, respectively, P<0.05). These results indicate the specific binding of HSA-FA to the folate receptor.

Key words: Folate receptor, Human serum albumin-folate conjugate, 99mTc-HSA-FA, Biodistribution