Localization of indium-111 in human malignant tumor xenografts and control by chelators.
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.
Watanabe
N
N
Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba, Japan. w_nao@nirs.go.jp
Oriuchi
N
N
Endo
K
K
Inoue
T
T
Tanada
S
S
Murata
H
H
Kim
E E
EE
Sasaki
Y
Y
D000818:Animals; D002118:Calcium / Q000097:blood; D002614:Chelating Agents / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007204:Indium / Q000097:blood / Q000493:pharmacokinetics; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D004369:Pentetic Acid / Q000494:pharmacology*; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D002614:Chelating Agents; D007205:Indium Radioisotopes; D007204:Indium; C020758:indium trichloride; D004369:Pentetic Acid; D004492:Edetic Acid; D002118:Calcium