The kinetics of soluble
indium-111 ((111)In) in human malignant
tumor xenografts and cells was investigated in combination with
chelators. Firstly, without
chelator, the kinetics of (111)In-chloride was investigated in vitro and in vivo using four human malignant
neuroblastoma SK-N-MC, pulmonary
papillary adenocarcinoma NCI-H441, pulmonary
squamous cell carcinoma PC 9, and
colon adenocarcinoma LS 180 cells and xenografts. (111)In was incorporated into
tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant
tumors xenografted into nude mice at 24 h postinjection of (111)In-chloride. Secondly, the effect of
edetate calcium disodium (CaNa2EDTA) on radioactivity in (111)In-labeled
tumors xenografts and cells was studied in vitro and in vivo. CaNa2EDTA significantly reduced (111)In-activity from the labeled
tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa2EDTA on radioactivity in human malignant
tumors xenografted into nude mice injected with (111)In-chloride was investigated. In one group of mice CaNa2EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of (111)In-chloride (postadministration), the localization of (111)In at the
tumors was significantly decreased at 72 h compared with the control in all four
tumor types. In the other group of mice, CaNa2EDTA administered intraperitoneally at 12 and 1 h before injection of (111)In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of
tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa3DTPA had a more powerful effect than CaNa2EDTA. In conclusion, (111)In-activity in
tumors consists of intracellular and extracellular components, and the extracellular (111)In may be cleared by
chelators. Pre- and postadministration of CaNa3DTPA could remove (111)In-nonspecific localization in
tumors when (111)In is released from the radiolabeled agents.