*Purpose: Acute cellular rejection (ACR) remains a clinically important problem following organ transplantation. Clinically, suspicion of ACR is dependent upon serum laboratory values, and diagnosis requires an invasive biopsy which carries risks of bleeding, graft loss, and sampling error. The aim of this study was to develop a non-invasive method of detecting ACR utilizing whole-body Immuno-PET imaging targeting CD122, a critical T cell activation marker.

*Methods: We utilized a murine model of MHC mismatched skin transplantation (Balb/C -> C57BL/6) in which mice received either no treatment or co-stimulation blockade (CoB). At day 10 post-transplantation, a copper-64 labeled anti-CD122 probe was injected intravenously followed by Immuno-PET imaging. SUV values of rejecting allografts (no treatment) were compared to non-rejecting allografts (CoB). We then performed Immuno-PET imaging in a non-human primate model of allogeneic kidney transplantation using a gallium-68 labeled anti-CD122 probe to minimize radiation exposure due to the shortened half-life of gallium-68. Three NHP underwent renal transplantation and were treated with CoB. All three animals underwent whole-body Immuno-PET imaging at both “early” (day 5-12) and “late” time points post-transplant (day 30-33).

*Results: SUV values of rejecting murine skin allografts were significantly greater than those treated with CoB (median SUV 108 vs. 35, p=0.001**). Immuno-PET findings correlated with increased CD122+ expression on CD8+ T cells in the blood, spleen and draining lymph nodes (dLN) of rejecting mice as well as histological analysis. In NHP, 2/3 renal transplant recipients experienced ACR by day 37, associated with an acute rise in serum creatinine. At day 30, despite a normal serum creatinine, Immuno-PET imaging revealed a significant increase in kidney SUV/cm³ compared to their respective early time point (day 5). The increase in kidney SUV/cm³ (Δ kidney SUV/cm³) between early and late time points in rejecting animals was associated with an increase in circulating CD122⁺ memory CD8⁺ T cells as well as histological changes. In comparison, 1/3 renal transplant recipient maintained a normal creatinine throughout the experimental period (>60 d) and had no change in Δ kidney SUV/cm³ as well as no significant increase in peripheral CD122⁺ memory CD8⁺ T cells.

*Conclusions: By targeting CD122+ T cells, Immuno-PET imaging provides a non-invasive method to detect ACR.

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