Noninvasive Radionuclide Molecular Imaging of the CD4-Positive T Lymphocytes in Acute Cardiac Rejection

Heart transplantation (HT) is an effective treatment for end-stage heart disease. However, acute rejection (AR) is still the main cause of death within one year after HT. AR is an acute immune response mediated by T lymphocytes, mainly CD4+ T lymphocytes. This study innovatively develops a radiolabeled probe ^99mTc-HYNIC-mAb_CD4 for noninvasive visualization of CD4+ T lymphocyte infiltration and detection of AR. The ^99mTc-HYNIC-mAb_CD4 and its isotype control ^99mTc-HYNIC-IgG were successfully prepared and characterized. The specificity and affinity of the probe in vitro were assessed by cell-binding experiments. Binding of ^99mTc-HYNIC-mAb_CD4 to CD4+ T lymphocytes was higher than that of the macrophages and IgG probe groups, and mAb_CD4 was effective in the blockade of the binding reaction. The biodistribution data confirmed the SPECT/CT images, with significantly higher levels of ^99mTc-HYNIC-mAb_CD4 observed in allografts compared to allograft treatment (10 mg/kg/d Cyclosporin A subcutaneously for 5 consecutive days after surgery), isografts, or in rats which received allografts injected with ^99mTc-HYNIC-IgG. Histological examination confirmed more CD4+ T lymphocyte infiltration in the allograft hearts than other groups. In summary, ^99mTc-HYNIC-mAb_CD4 achieved high affinity and specificity of binding to CD4+ T lymphocytes and accumulation in the transplanted heart. Radionuclide molecular imaging with ^99mTc-HYNIC-mAb_CD4 may be a potential diagnostic method for acute cardiac rejection.