Uptake and distribution of specific and control monoclonal antibodies in subcutaneous xenografts following intratumor injection.

Nude mice bearing s.c. xenografts of the human colon adenocarcinoma HT29 were given intratumor injections of a mixture of 125I-labeled specific antibody (AUA1) and 131I-labeled control antibody (HMFG1), or with the labels reversed. After dissection at 1 and 4 h postadministration, both specific and control antibodies had 47-63% of the injected dose (% ID) in the tumor. By 24 h, the tumor contained 43 +/- 11% ID of AUA1 which persisted at around this level for 5 days and remained at nearly 20% ID at 18 days. In contrast, the HMFG1 activity was 23 +/- 9% ID at 24 h, which continued to fall and was less than 5% ID by 7 days. Normal organ levels were less than 2% ID/g for both antibodies, with HMFG1 being higher than AUA1 at all times, resulting in specificity indices greater than 20 by 5 days. Autoradiography of tumors removed 2 h postinjection of 125I-labeled AUA1 or HMFG1 showed high levels of antibody at the injection site. At 48 h and 7 days postinjection, the specific antibody was bound to the surface of tumor cells in islands remote from the injection site, whereas the control antibody was found only in the stroma and blood vessels, or as diffuse nonspecific uptake. These data indicate that intratumor injection of radiolabeled monoclonal antibodies may achieve high radiation doses in accessible tumors without systemic irradiation.