Tumor uptake of radioiodinated anti-human pulmonary surfactant-associated protein monoclonal antibody PE10 in nude mice bearing human pulmonary adenocarcinoma in combination with an unlabeled preload

摘要

This study assessed the potential use of radioimmunoscintigraphy of pulmonary alveolar Type II cells tumor with the radiolabeled anti human surfactant associated protein (SP) monoclonal antibody (MAb) PE 10 in combination with preloads of unlabeled MAb. The in vitro binding of iodine-125 (I-125)-labeled MAb PE 10 (1 mug), which had a specific radioactivity of 400 MBq/mg, on human pulmonary papillary adenocarcinoma NCI-H441 cells that produced SP was investigated. In NCI-H441 tumor-bearing nude mice, the tumor uptake of I-125-MAb PE 10 (5 mug) was examined in combination with preloads of unlabeled MAb PE 10 (0, 5, 10, and 50 mug). An isotype matched unassociated murine MAb was used as a control both in vitro and in vivo. I-125-MAb PE 10 showed specific cell binding compared with I-125 control MAb. Tumor uptake of I-125-MAb pE 10 in vivo reached a peak of 4.97 +/- 0.33% injected dose per gram (%ID/g) at 48 h postinjection. Preloads of 5 and 10 mug unlabeled MAb PE 10 significantly enhanced tumor uptake at 48 h postinjection (5.94 +/- 0.29% ID/g and 5.72 +/- 0.29% ID/g, respectively), whereas preload of 50 mug unlabeled MAb PE 10 significantly decreased tumor uptake (2.75 +/- 0.32% ID/g) at 48 h. Preload of 5 mug unlabeled MAb PE 10 significantly increased the tumor-to-blood radioactivity ratio at 48 h (2.39 +/- 0.16). Preloads of unlabeled control MAL, did not cause any significant change in tumor uptake. Immunohistochemistry showed the intracellular and pericellular patterns of SP expression in tumor cells. In conclusion, radioimmunoscintigraphy with MAb PE 10 labeled with a gamma -emitting radioiodine such as I-123 might be a useful means of targeting pulmonary alveolar Type II tumor cells in combination with preloading with an optimal dose of the unlabeled MAb. NUCl MED BIOL 27;8:723-731, 2000. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 21]