Radiolabelled Nanoparticles for Diagnosis and Treatment of Cancer

Cancer is one of the leading cause of death worldwide.1 In 2010, a total of 1,529,560 new cancer cases and 569,490 cancer deaths were estimated in the United States alone.1 Despite advances in our understanding of tumor biology, cancer biomarkers, surgical procedures, radioand chemotherapy, the overall survival rate from cancer has not improved significantly in the past two decades. Early detection, pathological characterization, and individualized treatments are recognized as important aspects for improving the survival of cancer patients. Many novel approaches, such as imaging for the early detection of molecular events in tumors, comprehensive and personalized treatments, and targeted delivery of therapeutic agents to tumor sites, have been developed by various research groups; and some of these are already in clinical trials or applications for cancer patients. Radiation therapy, in conjunction with chemotherapy and surgery, is an effective cancer treatment option, especially for radiation-sensitive tumors. Radiation therapy utilizes high dose ionizing radiation to kill cancer cells and prevent progression and recurrence of the tumor. Traditionally, radiation therapies fall into one of three categories: external radiation, internal radiation and systemic radiation therapy. External radiation therapy delivers high-energy x-rays or electron or proton beams to a tumor from outside the body, often under imaging guidance. Internal radiation therapy (also called brachytherapy) places radiation sources within or near the tumor using minimally invasive procedures. Systemic radiation therapy delivers soluble radioactive substances, either by ingestion, catheter infusion, or intravenous administration of tumor-targeting carriers, such as antibodies or biocompatible materials, which carry selected radioisotopes. Although systemic radiation offers desirable advantages of improved efficacy as well as potentially reducing radiation dosage and side effects, in vivo delivery of radioisotopes with tumor targeted specificity needs to address many challenges that include: (i) the selection of radioisotopes with a proper half life; (ii) a delivery vehicle that can carry an optimal amount of radioisotopes and has favorable pharmacokinetics; (iii) suitable tumor biomarkers that can be used to direct the delivery vehicle into cancer cells; and (iv) specific tumor targeting ligands that are inexpensive to produce and can be readily conjugated to the delivery vehicles. In addition, a multifunctional carrier that not only delivers radioisotopes but also provides imaging capability for tracking and quantifying radioisotopes that have accumulated in the tumor is highly desirable.2