Perfluoro-15-crown-5 ether-labeled dendritic cells

Excerpt

Dendritic cells (DCs), known as antigen-presenting cells, are found in almost all peripheral tissues and in primary/secondary lymphoid organs (1). DCs are the initiator and modulator in the adaptive immune responses against bacteria, viruses, allergens, and tumor antigens (2). DCs in peripheral tissues are responsible for the capture of antigens (3). In the absence of inflammation, DCs remain in an immature state. The captured antigens are transported with DCs to the lymph node, but no co-stimulatory activation to T cells occurs. In the presence of inflammation, numerous mature DCs migrate to the draining lymph nodes. During migration, the antigens are processed into small peptides bound to the major histocompatibility complex (MHC) on the surface of the DCs. At the lymph nodes, mature DCs present the MHC-peptide complex to naïve T cells (CD4⁺ T helper cells and cytolytic CD8⁺ T cells) to activate them. After activation, a series of immune responses are completed through the interactions of T cells with other cells and molecules such as B cells for antibody formation, macrophages for cytokine releases, and targets for lysis (1). Behaving as mobile sentinels, DCs bring antigens to T cells and express co-stimulators to induce immunity. DCs have been used in many clinical trials to treat cancers and immunological disorders (4). Because the migratory properties of DCs are directly related to their function (5), non-invasive tracking of DCs becomes very important to clinic applications (2).

Being the only stable isotope of fluorine, with a natural abundance of ~100%, ¹⁹F has a nuclear spin 1/2 with a large gyromagnetic ratio (γ ~40.05 MHz/T) (6). The small γ difference between the ¹⁹F and ¹H (~6%) allows the use of existing proton nuclear magnetic resonance (NMR) instrumentation with minor adjustments to detect fluorinated species at high sensitivity (~83% relative to ¹H). Endogenous fluorine in vivo is found primarily in bones and teeth as solid fluorides, which have very short T₂ relaxation times and result in an undetectable signal with NMR imaging. Therefore, exogenously administered fluorinated tracers can be used to track various biological processes in vivo. For example, perfluorocarbons (PFCs) are used to measure oxygen tensions in tissues and tumors (7). The lack of background ¹⁹F signal is advantageous in in vivo applications, but additional ¹H images are required to provide anatomic interpretations. PFCs are extremely hydrophobic and do not dissolve in blood directly; they normally are formulated as biocompatible emulsions for intravenous administration (6). Inside the body, the PFC particles are cleared from circulation by phagocytes/macrophages or by respiration within several hours or days, depending on the administered dose, particle size, and PFCs (8). Many commercial PFC emulsions have been found to be nontoxic or do not cause any health problems other than tissue swelling (6). Perfluoro-15-crown-5 ether (perfluoropolyether, PFPE), a commonly used PFC, contains 20 equivalent ¹⁹F spins that generate a single resonance (-92.5 ppm) in NMR imaging (9). This singlet simplifies its images such that no chemical shift–induced artifact is expected. PFPE can be emulsified to form particles of ~100–200 nm in diameter, allowing for cellular uptake via endocytosis (4). DCs are labeled with PFPE (PFPE-DCs) for ¹⁹F magnetic resonance imaging (MRI).