Radiolabeled lipid nanoparticles for diagnostic imaging.

Background: Nanoparticles are increasingly being incorporated into the design of diagnostic imaging agents. Significant research efforts have been conducted with one class of lipid nanoparticle (liposomes) radiolabeled with gamma-emitting radionuclides as radiopharmaceuticals for scintigraphic imaging of cancer, inflammation/infection and sentinel lymph node detection.

Objective: This article reviews the current literature with special emphasis on the clinical studies performed with liposome radiopharmaceuticals for detection of tumors, infectious/inflammatory sites or metastatic lymph nodes. Future uses of liposome radiopharmaceuticals are also described.

Methods: Characteristics required of the radionuclide, liposome formulation and radiolabeling method for an effective radiopharmaceutical are discussed. A description of the procedures and instrumentation for conducting an imaging study with liposome radiopharmaceutical is included. Clinical studies using liposome radiopharmaceuticals are summarized. Future imaging applications of first- and second-generation radiolabeled liposomes for chemodosimetry and the specific targeting of a disease process are also described.

Results/conclusion: The choice of radionuclide, liposome formulation and radiolabeling method must be carefully considered during the design of a liposome radiopharmaceutical for a given application. After-loading and surface chelation methods are the most efficient and practical. Clinical studies with liposome radiopharmaceuticals demonstrated that a wide variety of tumors could be detected with good sensitivity and specificity. Liposome radiopharmaceuticals could also clearly detect various soft tissue and bone inflammatory/infectious lesions, and performed equal to or better than infection imaging agents that are approved at present. Yet, despite these favorable results, no liposome radiopharmaceutical has been approved for any indication. Some of the reasons for this can be attributed to reports of an unexpected infusion-related adverse reaction in two studies, the requirement of more complex liposome manufacturing procedures, and the adoption of other competing imaging procedures. Continued research of liposome radiopharmaceutical design based on a better understanding of liposome biology, improved radiolabeling methodologies and advances in gamma camera technology is warranted.