Noninvasive methods to image the trafficking of phenotypically defined immune cells are paramount as we attempt to understand adaptive immunity. A ¹⁹F MRI‐based methodology for tracking and quantifying cells of a defined phenotype is presented. These methods were applied to a murine inflammation model using antigen‐specific T cells. The T cells that were intracellularly labeled ex vivo with a perfluoropolyether (PFPE) nanoemulsion and cells were transferred to a host receiving a localized inoculation of antigen. Longitudinal ¹⁹F MRI over 21 days revealed a dynamic accumulation and clearance of T cells in the lymph node (LN) draining the antigen. The apparent T‐cell numbers were calculated in the LN from the time‐lapse ¹⁹F MRI data. The effect of in vivo T‐cell division on the ¹⁹F MRI cell quantification accuracy was investigated using fluorescence assays. Overall, in vivo cytometry using PFPE labeling and ¹⁹F MRI is broadly applicable to studies of whole‐body cell biodistribution. Magn Reson Med, 2009.

Inflammatory disease management poses challenges due to the complexity of inflammation and inherent patient variability, thereby necessitating patient-specific therapeutic interventions. Theranostics, which integrate therapeutic and imaging functionalities, can be used for simultaneous imaging and treatment of inflammatory diseases. Theranostics could facilitate assessment of safety, toxicity and real-time therapeutic efficacy leading to personalized treatment strategies. Macrophages are an important cellular component of inflammatory diseases, participating in varied roles of disease exacerbation and resolution. The inherent phagocytic nature, abundance and disease homing properties of macrophages can be targeted for imaging and therapeutic purposes. This review discusses the utility of theranostics in macrophage ablation, phenotype modulation and inhibition of their inflammatory activity leading to resolution of inflammation in several diseases.

Our recent studies have demonstrated that human immature dendritic cells (DCs) are able to directly and effectively mediate apoptotic killing against a wide array of cultured and freshly-isolated cancer cells without harming normal cells. In the present study, we demonstrate that this tumoricidal activity is mediated by multiple cytotoxic TNF family ligands. We determine that human immature DCs express on their cell surface four different cytotoxic TNF family ligands: TNF, lymphotoxin-α₁β₂, Fas ligand, and TNF-related apoptosis inducing ligand; while cancer cells express the corresponding death receptors. Disruptions of interactions between the four ligands expressed on DCs and corresponding death-signaling receptors expressed on cancer cells using specific Abs or R:Fc fusion proteins block the cytotoxic activity of DCs directed against cancer cells. The novel findings suggest that DC killing of cancer cells is mediated by the concerted engagement of four TNF family ligands of DCs with corresponding death receptors of cancer cells. Overall, our data demonstrate that DCs are fully equipped for an efficient direct apoptotic killing of cancer cells and suggest that this mechanism may play a critical role in both afferent and efferent anti-tumor immunity.

Current diagnosis of organ rejection following transplantation relies on tissue biopsy, which is not ideal due to sampling limitations and risks associated with the invasive procedure.We have previously shown that cellular magnetic resonance imaging (MRI) of iron‐oxide labeled immune‐cell infiltration can provide a noninvasive measure of rejection status by detecting areas of hypointensity on T‐weighted images. In this study, we tested the feasibility of using a fluorine‐based cellular tracer agent to detect macrophage accumulation in rodent models of acute allograft rejection by fluorine‐19 (¹⁹F) MRI and magnetic resonance spectroscopy. This study used two rat models of acute rejection, including abdominal heterotopic cardiac transplant and orthotopic kidney transplant models. Following in vivo labeling of monocytes and macrophages with a commercially available agent containing perfluoro‐15‐crown‐5‐ether, we observed ¹⁹F‐signal intensity in the organs experiencing rejection by ¹⁹F MRI, and conventional ¹H MRI was used for anatomical context. Immunofluorescense and histology confirmed macrophage labeling. These results are consistent with our previous studies and show the complementary nature of the two cellular imaging techniques. With no background signal, ¹⁹F MRI/magnetic resonance spectroscopy can provide unambiguous detection of fluorine labeled cells, and may be a useful technique for detecting and quantifying rejection grade in patients. Magn Reson Med, 2011.