Assessment of in vivo natural antitumor resistance and lymphocyte

Clearance of IV-injected tumor cells has been correlated with levels of natural killer (NK) cell activity in recipient animals. Studies of in vivo tumor cell clearance strongly suggest a relationship between levels of NK cell activity and antitumor or antimetastatic effector function. This study outlines the applicability of three radiolabels, 125I]iododeoxyuridine, ( 125I]dUrd), indium-111-oxine chelate ( 111In]Ox), and chromium-51 (51Cr), to studies of tumor cell clearance in vivo. The suitability of these labels for analysis of the in vivo migration patterns of normal lymphocytes or thymus-derived T cells cultivated in vitro (CTC) is also discussed. The results indicate that 111In]Ox and 51Cr compare favorably with the more widely used 125]dUrd as radiolabels for the assessment of IV-injected tumor cell clearance from the lungs of mice. The rates of clearance of both 111In]Ox and 51Cr, like that for 125I]dUrd, correlate closely with levels of NK-cell activity of the host. Further studies with 111In]Ox reveal that treatment of recipients with anti-asialo GM1 serum, a regimen known to suppress NK-cell activity, demonstrates the appropriate reduction in isotope clearance from the lungs after NK suppression. However, clearance data obtained by monitoring levels of radioactivity in the liver after IV injection must be viewed cautiously, since the same cells labeled with 111In]Ox and 125I]dUrd had a different pattern of clearance from the liver. The same inconsistencies in clearance were observed when 111In]Ox and 125I]dUrd were injected intrafootpad (i.f.p.). Similar effects were observed when 111In]Ox or 51Cr was applied to studies of CTC migration. Levels of 111In]Ox and 51Cr remained high in the liver after IV injection, while 125I]dUrd was rapidly cleared. Normal spleen or thymic lymphocytes exhibited the expected homing to the spleen after labeling with 111In]Ox, indicating a suitability of this label for migration studies, except possibly in the liver. These results with CTC and normal lymphocytes should be considered during the formulation of immunotherapy protocols based on cell migration data, since the choice of radiolabel can result in widely divergent levels of radioactivity accumulated in some organs, and may not provide an accurate representation of the presence of viable, intact, or functional cells.