Detection of homing, proliferation, and infiltration sites of adult T cell leukemia cells in severe combined immunodeficiency mice using radiometric techniques.

To clarify the mechanism of in vivo proliferation of adult T cell leukemia (ATL) cells, we examined the organ distribution of ATL-43T cell line cells derived from original leukemic cells in severe combined immunodeficiency (SCID) mice using radiometric techniques. First, we injected 111In-oxine-labeled ATL-43T cells into SCID and CB17 mice. On day 6, significant accumulation of radioactivity was found in the spleen and thymus of SCID mice (33.3 +/- 9.4 and 10.0 +/- 3.6% injected dose/g of tissue [%ID/g], respectively) in comparison with that in CB17 mice (19.1 +/- 2.5 and 3.7 +/- 0.9%ID/g, respectively). Next, we injected radiolabeled anti-Tac monoclonal antibody (MoAb) recognizing human interleukin-2 receptor (IL-2R) alpha chain or isotype-matched control MoAb RPC5 in SCID mice bearing ATL-43T cells 4 weeks after cell inoculation. The amounts of radioactivity found in the spleen and thymus of SCID mice injected with 125I-labeled anti-Tac MoAb (22.5 +/- 6.9 and 22.8 +/- 9.6 %ID/g, respectively) were significantly higher than those in the corresponding organs of SCID mice injected with 125I-labeled RPC5 MoAb (12.0 +/- 5.1 and 7.5 +/- 4.6 %ID/g, respectively). Similar results were obtained with 111In-labeled anti-Tac MoAb. These results were consistent with the histological findings of SCID mice bearing ATL-43T cells, indicating that ATL-43T cells infiltrated preferentially into the lymphoid organs, such as the spleen and thymus, and proliferated there. Thus, the radiometric techniques employed in this study were very useful to evaluate the proliferation sites of ATL-43T cells in SCID mice. Furthermore, this murine model could give us an opportunity to test the feasibility of therapeutic application of radiolabeled anti-Tac MoAb.