Intratumoral Injection of (188)Re labeled Cationic Polyethylenimine Conjugates: A Preliminary Report

ABSTRACT

(188)Re(Rhenium) is easily obtained from an in-house (188)W/(188)Re generator that is similar to the current (99)Mo/(99m)Tc generator, making it very convenient for clinical use. This characteristic makes this radionuclide a promising candidate as a therapeutic agent. Polyethylenimine (PEI) is a cationic polymer and has been used as a gene delivery vector. Positively charged materials interact with cellular blood components, vascular endothelium, and plasma proteins. In this study, the authors investigated whether intratumoral injection of (188)Re labeled transferrin (Tf)-PEI conjugates exert the effect of radionuclide therapy against the tumor cells. When the diameters of the Ramos lymphoma (human Burkitt's lymphoma) xenografted tumors reached approximately 1 cm, 3 kinds of (188)Re bound compounds (HYNIC-PEI-Tf, HYNIC-PEI, (188)Re perrhenate) were injected directly into the tumors. There were increases in the retention of (188)Re inside the tumor when PEI was incorporated with (188)Re compared to the use of free 188Re. The (188)Re HYNIC-Tf-PEI showed the most retention inside the tumor (retention rate=approximately 97%). H&E stain of isolated tumor tissues showed that (188)Re labeled HYNIC-PEI-Tf caused extensive tumor necrosis. These results support (188)Re HYNIC-PEI-Tf as being a useful radiopharmaceutical agent to treat tumors when delievered by intratumoral injection.