A novel probe for the non-invasive detection of tumor-associated inflammation

Abstract

A novel dual-mode contrast agent was formulated through the addition of an optical near infrared (NIR) probe to a perfluorocarbon (PFC)-based 19F magnetic resonance imaging (MRI) agent, which labels inflammatory cells in situ. A single PFC-NIR imaging agent enables both a qualitative, rapid optical monitoring of an inflammatory state and a quantitative, detailed and tissue-depth independent magnetic resonance imaging (MRI). The feasibility of in vivo optical imaging of the inflammatory response was demonstrated in a subcutaneous murine breast carcinoma model. Ex vivo optical imaging was used to quantify the PFC-NIR signal in the tumor and organs, and results correlated well with quantitative 19F NMR analyses of intact tissues. 19F MRI was employed to construct a three-dimensional image of the cellular microenvironment at the tumor site. Flow cytometry of isolated tumor cells was used to identify the cellular localization of the PFC-NIR probe within the tumor microenvironment. Contrast is achieved through the labeling of host cells involved in the immune response, but not tumor cells. The major cellular reservoir of the imaging agent were tumor-infiltrating CD11b+ F4/80low Gr-1low cells, a cell subset sharing immunophenotypic features with myeloid-derived suppressor cells (MDSCs). These cells are recruited to sites of inflammation and are implicated in immune evasion and tumor progression. This PFC-NIR contrast agent coupled to non-invasive, quantitative imaging techniques could serve as a valuable tool for evaluating novel anticancer agents.

Noninvasive Imaging of Early Venous Thrombosis by 19 F Magnetic Resonance Imaging With Targeted Perfluorocarbon Nanoemulsions

“…Until now, 19 F MRI has been used predominantly for immune cell tracking in a variety of clinically relevant inflammation models. [21][22][23][24][25][26][27][28][29] This approach is based on the rapid uptake of intravenously injected PFCs by circulating monocytes that subsequently migrate into the inflamed area, resulting in a local accumulation of 19 F-loaded immune cells. In the present study, we report a novel procedure for the generation of targeted PFCs that makes use of a sterol-based postinsertion technique (SPIT) to generate α2-antiplasminlabeled PFCs (α2 AP -PFCs).…”

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

“…Overall, the vast majority of studies that perform cell tracking with 19 F MRI have employed spin echo sequences. [16][17][18][19][37][38][39][40] Using the 3D bSSFP sequence, we injected and detected 1.5×10 6 Cell Sense-labeled hMSC in vivo on day 0 using a spatial resolution of 2 mm 3 (2 µL). If we assume that on day 0 all of the injected cells are present and evenly distributed, then we detected 30,000 cells per voxel.…”

“…Examples of 19 F MR imaging performed to date include: monitoring inflammation (tumor models, rheumatoid arthritis, lung injuries, and after ischemia in the lung or brain), [16][17][18][19] detection of T cell and dendritic cell migration, 20,21 and tracking the fate of transplanted hematopoietic and neural stem cells.…”

Nanosized Camptothecin Conjugates for Single and Combined Drug Delivery

“…Nanotechnology has achieved huge accomplishments in the past few decades, providing scientists with lots of techniques to fabricate nanoparticles for different objectives (14)(15)(16)(17)(18)(19)(20)(21)(22). From either top-down or bottom-up methods, we are now able to prepare nanoparticles with different shapes, sizes and chemical-physical properties both inside and outside (23)(24)(25)(26).…”