Current approaches to detect and diagnose rejection are retrospective and/or invasive. These methods assess the extent of end organ damage by insensitive and non-specific measures (e.g. Creatinine), or assess graft immune cell infiltrate and organ damage by costly and risky invasive biopsy. The need for early non-invasive detection of alloreactivity prior to organ damage has never been greater. Recently we reported development of a technique to track immune cell subsets during viral infection and T cell depletion in rhesus macaques (Science 2016, Nature Methods 2015). This technique, Immuno-PET (Positron Emission Tomography), allows for whole-body visualization of immune cell subsets with radiolabeled monoclonal antibody or fragments (mAbs) specific for cell surface markers such as CD4.We adapted ImmunoPET for detection of alloreactive T cells. PET is a clinical mainstay for the detection of cancer, using radiolabeled probes to monitor target tissues. We recently described a critical role for CD122 the shared IL2/IL15Rβ, in alloreactivity. CD122 is highly expressed on alloreactive T cells during rejection. T cell infiltrate within the allograft expresses high levels of CD122. We demonstrate the utility of ImmunoPET to sensitively and specifically monitor whole T cell distribution in both mice and non-human primates, and extended this application to detection of alloreactivity using CD122 and CD44 directed probes (Fig 2 ). We found significant increase in SUV (Standard Uptake Value) in spleen, draining lymph nodes, and graft of transplanted animals that correlated with absolute numbers of T cells expressing CD122 or CD44, demonstrating ImmunoPET's fidelity and versatility.

CITATION INFORMATION: Mathews D, Lindsay K, Santangelo P, Dong Y, Tso J, Adams A. Non-Invasive Detection of Rejection with ImmunoPET Imaging. Am J Transplant. 2017;17 (suppl 3).

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