BACKGROUND: The diagnosis of cardiac allograft rejection is based on routine endomyocardial biopsy. To study an alternative method the authors evaluated the migration and scintigraphic imaging of Indium-111-labelled lymphocytes in a model of acute heart allograft rejection. METHODS AND RESULTS: Cervical heterotopic heart transplantation was performed in 10 dogs. Blood samples were harvested at 24 and 48 h after surgery for labelling of 36+/-6x10(6) lymphocytes with 6.62+/-0.56 MBq of Indium-111. Daily blood samples and heart biopsies were obtained for nuclear counting on the next three days; animals were sacrificed and both donor and native hearts were studied. Between 20 and 31% of autologous labelled lymphocytes remained in circulation until 72 h after injection. Maximal plasma Indium-111 activity was 315+/-90 compared with 5513+/-1483 cpm/mL in whole blood (P<0.05). An average of 10,176+/-3444 labelled lymphocytes per gram of tissue were present in allograft biopsies while histological evaluation showed mild to moderate acute rejection. The ratio of tissue biopsy to blood Indium-111 counts varied from 0.7+/-0.2, 6 h after autologous injection to 8.5+/-3.8 48 h later (P<0.05). At autopsy, 298+/-66 labelled celts per gram of tissue were present in native hearts compared with 2686+/-711 in allografts (P<0.05). Scintigraphic imaging using holospectral acquisition was performed; six lateral projections showed an indium activity ratio (transplanted heart to background tissue) of 2.8, 24 to 72 h after autologous injection of labelled cells. CONCLUSIONS: Labelling of a small number of lymphocytes with Indium-111 gave a stable population of circulatory lymphocytes for studying migration of labelled cells into allografts and a noninvasive scintigraphic approach to diagnose cardiac allograft rejection.