Development of novel tumor-targeted theranostic nanoparticles activated by membrane-type matrix metalloproteinases for combined cancer magnetic resonance imaging and therapy.

A major drawback with current cancer therapy is the prevalence of unrequired dose-limiting toxicity to non-cancerous tissues and organs, which is further compounded by a limited ability to rapidly and easily monitor drug delivery, pharmacodynamics and therapeutic response. In this report, the design and characterization of novel multifunctional "theranostic" nanoparticles (TNPs) is described for enzyme-specific drug activation at tumor sites and simultaneous in vivo magnetic resonance imaging (MRI) of drug delivery. TNPs are synthesized by conjugation of FDA-approved iron oxide nanoparticles ferumoxytol to an MMP-activatable peptide conjugate of azademethylcolchicine (ICT), creating CLIO-ICTs (TNPs).

Intravenous ferumoxytol allows noninvasive MR imaging monitoring of macrophage migration into stem cell transplants.

Purpose: To develop a clinically applicable imaging technique for monitoring differential migration of macrophages into viable and apoptotic matrix-associated stem cell implants (MASIs) in arthritic knee joints.

Materials And Methods: With institutional animal care and use committee approval, six athymic rats were injected with intravenous ferumoxytol (0.5 mmol iron per kilogram of body weight) to preload macrophages of the reticuloendothelial system with iron oxide nanoparticles.

Differentiation of normal thymus from anterior mediastinal lymphoma and lymphoma recurrence at pediatric PET/CT.

Purpose: To evaluate the role of positron emission tomography (PET)/computed tomography (CT) in the differentiation of normal thymus from mediastinal lymphoma and lymphoma recurrence in pediatric patients.

Materials And Methods: The study was approved by the institutional review board, and informed consent was waived. The study was HIPAA compliant.

Labeling stem cells with ferumoxytol, an FDA-approved iron oxide nanoparticle.

Stem cell based therapies offer significant potential for the field of regenerative medicine. However, much remains to be understood regarding the in vivo kinetics of transplanted cells. A non-invasive method to repetitively monitor transplanted stem cells in vivo would allow investigators to directly monitor stem cell transplants and identify successful or unsuccessful engraftment outcomes.

MRI of tumor-associated macrophages with clinically applicable iron oxide nanoparticles.

Purpose: The presence of tumor-associated macrophages (TAM) in breast cancer correlates strongly with poor outcome. The purpose of this study was to develop a clinically applicable, noninvasive diagnostic assay for selective targeting and visualization of TAMs in breast cancer, based on magnetic resonanceI and clinically applicable iron oxide nanoparticles.

Experimental Design: F4/80-negative mammary carcinoma cells and F4/80-positive TAMs were incubated with iron oxide nanoparticles and were compared with respect to magnetic resonance signal changes and iron uptake.

Labeling human embryonic stem-cell-derived cardiomyocytes for tracking with MR imaging.

Background: Human embryonic stem cells (hESC) can generate cardiomyocytes (CM), which offer promising treatments for cardiomyopathies in children. However, challenges for clinical translation result from loss of transplanted cell from target sites and high cell death. An imaging technique that noninvasively and repetitively monitors transplanted hESC-CM could guide improvements in transplantation techniques and advance therapies.