Subchapter 1.4: Radiolabeled functional nanoparticles in preventive and regenerative medicine

Abstract

Nuclear medicine is a branch of medicine that uses radiation to provide infor¬mation about the functioning of a person’s specific tissue/organs or to treat a disease. Radiolabeled nanoparticles (NPs) represent a new class of agents with a great potential for nuclear medicine applications. The key advantage of using radiolabeled NPs is that a very small amount can be used to obtain information of great importance.1 They may be used to detect and characterize disease, to deliver relevant therapeutics, and to monitor the therapeutic effect as well. Furthermore radiotracer-based imaging either using single-photon emission computed tomog¬raphy (SPECT) or positron emission tomography (PET) is particularly suited in the study of pharmacokinetic/pharmacodynamic parameters of nanomaterials and determination of their optimal nanodimensional architecture for tissue/organ re¬generation. Measuring radiation from radioactive tracers attached to NPs has been demonstrated to be a highly sensitive and specific method that allows accurate quantification, without limits to tissue penetration in any organ. Nuclear imaging approaches are highly suitable for detection, as they offer a high detection sensitiv¬ity at high temporal and spatial resolutions, requiring a radionuclide concentration of around 10−10 M at the site of interest.Nanoparticulate agents typically demonstrate pharmacokinetic behavior differ¬ent from that of small molecules2 and provide flexible platforms for integration of multiple functional entities, including targeting ligands, multiple types of contrast materials, and/or therapeutics. In contrast to traditional compounds used for radio¬pharmaceutical preparation, nanomaterials have an immense available surface area per unit of volume and tunable optical, electronic, magnetic, and biological proper¬ties. Generally, they can be tailored to meet the needs of specific applications and engineered to have different physicochemical properties that affect in vivo biodis¬tribution: sizes, shapes, chemical compositions, surface chemical characteristics, and hollow or solid structures.3 Efficient diagnosis/radiotherapy is provided through passive targeting based on the enhanced permeability and retention (EPR) effect and/or active targeting through the incorporation of a targeting moiety on an NP. Nontargeted NPs can accumulate in tumors, as the tumor vasculature is usually leaky and without lymphatic drainage. Active targeting is achieved by functionalizing the NPs surface with suitable vectors, including peptides, antibodies, and other biomolecules, which recognize characteristic epitopes at the surface of the diseased cells. Radiolabeled antibodies may effectively target even single cancer cells in circula¬tion5 or small cancer cell clusters,6 thereby enabling a more specific radiation dose delivery, preventing damage to healthy tissues.