Radiolabeled, folate-conjugated liposomes as tumor imaging agents: Formulation and in vitro evaluation

Abstract

Cancer is the major burden of disease worldwide. The folate receptor, as a specific tumor target, is over-expressed in many types of cancer including ovarian carcinomas, breast, colon, renal, and lung tumors. Nuclear medicine hybrid imaging modalities, such as SPECT/CT, provide both metabolic and anatomic information. Therefore, specific contrast agents are essentially needed. Liposomes are favorable systems with many advantages. The aim of this study was to formulate liposomal imaging agents for molecular tumor imaging by SPECT or SPECT/CT and evaluate their efficacy. Nanosized, polyethyleneglycolated, folate-conjugated and unmodified, diethylenetriaminepentaacetic acid-phosphatidylethanolamine containing, neutral and positively charged liposomes were formulated and characterized by mean particle size, zeta potential, and quantitative determination of the phospholipids in the liposomes. The binding of the synthetized imaging agents to 4T1 breast tumor cells was evaluated by fluorescence microscopy and radioactivity counting. Folate-conjugated neutral and positively charged liposomes were found to be effective as tumor imaging agents exhibiting an almost 3-fold increased uptake and brighter fluorescence microscopy images than unmodified ones in in vitro experiments using 4T1 breast tumor cells. These results could be considered as an important step towards the development of folate-specific agents for tumor imaging by SPECT and SPECT/CT.