Detection of cardiac transplant rejection with 111In-labeled lymphocytes and gamma scintigraphy.

BACKGROUND

Cardiac transplantation is an increasingly important treatment for patients with end-stage heart failure. Rejection is one of the major limitations, and currently, serial endomyocardial biopsies are required to diagnose rejection. In the year after transplantation, patients routinely undergo 12, 14, or more biopsies. Infiltration of lymphocytes into the graft is a central feature of rejection. Previous studies from our laboratory have demonstrated the feasibility of detecting early rejection noninvasively with gamma scintigraphy after administration of autologous lymphocytes labeled with 111In.

METHODS AND RESULTS

Eight patients were studied at the time of routine biopsy an average of 4.5 months after cardiac transplantation. Autologous lymphocytes were isolated and labeled with 111In. Forty-eight to 72 hours later, patients underwent planar scintigraphic imaging. Myocardial accumulation of labeled lymphocytes was quantified (indium excess, IE) with a previously described and validated technique. Animal studies have shown that an IE > or = 0.07 is associated with rejection. Two of four patients with biopsy grade 0 or 1A rejection had no excess accumulation of labeled lymphocytes. The other two patients with biopsy grade 0 or 1A had an average IE of 0.13 +/- 0.04 (SD), which may actually represent the higher sensitivity of the scintigraphic approach, since the whole myocardium is interrograted. All four patients with biopsy grade 1B rejection had increased accumulation of labeled lymphocytes (IE = 0.18 +/- 0.06, P = .06 compared with all patients with grade 0 or 1A biopsies).

CONCLUSIONS

The development of a sensitive, specific, and noninvasive method of diagnosing cardiac allograft rejection in humans might obviate the need for endomyocardial biopsy as well as improve the accuracy of diagnosis. The results suggest that scintigraphic detection of labeled lymphocytes is a promising approach for the noninvasive detection of cardiac transplant rejection. In addition, the approach should permit the assessment of the efficacy of antirejection therapy.