Stable water isotope labeling and magnetic resonance imaging for visualization of the presence of and prediction of the likelihood of occurence of rapidly dividing cells

#The present disclosure relates to systems, methods, and devices for the non-radioactive visualization of rapidly dividing cells using stable water isotope labeling followed by detection via stable isotope nuclear magnetic resonance imaging.

#The identification and treatment of diseases and/or conditions characterized by the presence of rapidly dividing cells is often delayed by the need to perform a biopsy before making an initial diagnosis. Performing a biopsy can be an invasive procedure, particularly when tissue must be collected from internal organs. By the time such a diagnosis is made, the disease or condition has progressed. For example, chronic graft-versus-host disease (cGVHD) is a prevalent and highly morbid condition affecting allogeneic hematopoietic stem cell transplant (“allogeneic HSCT” or “AHSCT”) recipients. Currently, there are no diagnostic imaging features or validated biomarkers predictive of impending or active cGVHD. It is known that biopsies performed on HSCT recipients are risky and difficult, as these patients are often on systemic immunosuppression.

#Early detection of cGVHD and other diseases or conditions characterized by the presence of rapidly dividing cells, such as cancer or infection, would likely improve the long-term prognosis of the patient. Non-invasive methods for such early detection are desirable to limit the need for invasive biopsies only to confirm initial findings and minimize additional physical impact on the patient.

#FIGS. 1A and 1B depict anatomical drawings of mice that received hematopoietic stem cell transplantation (HSCT), according to one embodiment;

#FIG. 2A is a graph depicting clinical scores relating to cGVHD symptoms for syngeneic HSCT recipients and allogeneic HSCT recipients, according to one embodiment.

#FIGS. 2B and C are photographs of mice at different time points post HSCT that correspond to the clinical scores for allogeneic HSCT recipients provided in FIG. 2A, according to one embodiment;

#Reference characters indicate corresponding elements among the view of the drawings. The headings used in the figures do not limit the scope of the claims.

#The present disclosure generally relates to the early detection of chronic graft-versus-host disease (cGVHD) and other diseases or conditions characterized by the presence of rapidly dividing cells, such as, but not limited to cancers, infections, and autoimmune diseases. In particular, the present disclosure describes improved systems and methods for labeling whole organisms, and/or organs, and/or cells with stable water isotopes, including hydrogen and oxygen, (i.e. deuterium (2H) and heavy oxygen (17O)) followed by magnetic resonance imaging for the stable water isotope (e.g. deuterium MRI (dMRI) and/or 17O MRI), for visualization of rapidly dividing cells. The present disclosure also relates to the use of deuterium and oxygen stable water isotopes as labeling agents for imaging patients post allogeneic hematopoietic stem cell transplantation (“allogeneic HSCT” or “AHSCT”) for diagnosing of early and/or ongoing cGVHD. While the systems and methods are primarily disclosed and described regarding the use of deuterium (2H), the systems and methods may be configured for use with either deuterium (2H), heavy oxygen (17O), or both. Other stable water isotopes may also be used. Stable water isotope MRI (swiMRI), as used herein, encompasses both, dMRI and 17O MRI. In one aspect, swiMRI may include the simultaneous imaging of deuterium and heavy oxygen. In other aspects, the stable water isotopes may be imaged separately.

#Rapidly dividing cells, as used herein, may include, but are not limited to, T cells and other immune cells that infiltrate target organs affected by cGVHD. In the various embodiments disclosed, swiMRI allows early detection of cGVHD in a non-radioactive and inexpensive manner, and allows for the diagnosis and monitoring of active or ongoing cGVHD. Alternatively, as deuterium preferentially incorporates into rapidly dividing cells, swiMRI may be used for non-invasive in vivo tumor imaging, including visualization of neoplastic/cancer cells. The systems and methods of the present disclosure offer inexpensive and non-radioactive alternatives to positron emission tomography (PET).