PET with ¹⁸F-FDG–Labeled T Lymphocytes for Diagnosis of Acute Rat Renal Allograft Rejection

Abstract

We proposed small-animal PET with 18 F-FDG-labeled T lymphocytes as a new method for image-based diagnosis of acute allogeneic renal transplant rejection (AR) established in a rat model. Methods: One and 2 h after tail vein injection of 30 · 10 6 ex vivo 18 F-FDG-labeled human T cells into male 10-wk-old uninephrectomized, allogeneically transplanted rats (aTX; Lewis-brown Norway [LBN] to Lewis), whole-body radioactivity distribution was assessed in vivo by small-animal PET (postoperative day 4), and percentage injected dose (%ID) as a parameter of T-cell infiltration was assessed and compared between graft and native kidney. In vivo results were confirmed by autoradiography and staining of human CD3 after postmortem dissection. Syngeneically transplanted rats (sTX) (LBN to LBN), rats with ischemia-reperfusion injury (IRI) (45-min warm ischemia), and rats subjected to acute cyclosporine A (CSA) toxicity (50 mg/kg for 2 d intraperitoneally) served as controls. Results: The accumulation of labeled cells was significantly elevated in allografts with AR (1.07 6 0.28 %ID), compared with native control kidneys (0.49 6 0.18 %ID) (P , 0.0001). No differences were found among native controls, sTX, CSA toxicity, and kidneys with IRI. In vivo uptake of 18 F-FDG cells measured in the PET scanner correlated with results obtained by autoradiography, histologic evaluation, and polymerase chain reaction. Conclusion: We proposed graft PET imaging using 18 F-FDG-labeled T cells as a new option to detect rat renal AR with a low dose of 18 F-FDG in a noninvasive, fast, and specific manner in rats.

Renal Contrast-Enhanced Sonography Findings in a Model of Acute Cellular Allograft Rejection

“…Recently, we demonstrated that molecular imaging targeting T cells not only detects AR but also reflects the degree of inflammation . Thus, we correlated the anti‐CD3 ultrasound signal intensity with the number of CD3 + cells per field of view as well as the mRNA expression of CD3 .…”

“…All surgical and imaging techniques were approved by a government committee on animal welfare and performed in accordance with national animal protection guidelines. Renal transplantation was performed simultaneously by two investigators as previously reported and described in detail elsewhere . In short, the left kidney including ureter, renal artery, and pieces of the abdominal aorta and the renal vein were explanted from age‐ and weight‐matched LBN or BN rats and implanted into uninephrectomized LEW rats (allogeneically transplanted [aTX]).…”

“…These include single‐photon emission computer tomography and positron emission tomography (PET). With this in mind, we established PET by using 18 F‐fluorodeoxyglucose ( 18 F‐FDG) and 18 F‐FDG–labeled T lymphocytes to assess AR in a rat renal transplantation model . Consistently, Lovinfosse et al have shown in a first clinical study that 18 F‐FDG PET/computed tomography may help to predict nonrejection to avoid unnecessary transplant biopsies .…”

SPECT- and PET-Based Approaches for Noninvasive Diagnosis of Acute Renal Allograft Rejection

“…In kidney-transplanted patients, scintigraphic analysis of 99m Tc-labelled mononuclear cells allowed diagnosis of AR and discrimination from acute tubular necrosis (ATN) [43]. In a more sophisticated approach with PET, human leukocytes, in particular human cytotoxic lymphocytes, marked with low amounts of 18 F-FDG ex vivo were applied in a rat kidney-transplant model [44]. Subsequent PET analysis led to the differential diagnosis of AR excluding other causes of early graft dysfunction such as ischemia, ATN, or immunosuppressive toxicity (Figure 2).…”

Have we forgotten imaging prior to and after kidney transplantation?

“…Citation rates show a similar trend, with a surge for all included publications, but a lower rate for publications combining imaging and KTX. Studies focusing on PET/CT for the diagnosis of acute allograft rejection showed significant associations in both acute rat renal allograft models and a clinical study, while the sensitivity remained too low for clinical applications [11][12][13][14].…”