Radionuclide imaging of tumor xenografts in mice using a gelatinase-targeting peptide
| Autor: | Oula Penate, Medina, Kalevi, Kairemo, Heli, Valtanen, Aino, Kangasniemi, Sami, Kaukinen, Ilona, Ahonen, Perttu, Permi, Arto, Annila, Mia, Sneck, Juha M, Holopainen, Sirkka-Liisa, Karonen, Paavo K J, Kinnunen, Erkki, Koivunen |
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| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Fibrosarcoma Transplantation Heterologous Technetium Matrix Metalloproteinase Inhibitors Peptides Cyclic Iodine Radioisotopes Mice Matrix Metalloproteinase 9 Liposomes Animals Humans Matrix Metalloproteinase 2 Protease Inhibitors Tissue Distribution Radiopharmaceuticals Radionuclide Imaging Sarcoma Kaposi Neoplasm Transplantation |
| Zdroj: | Anticancer research. 25(1A) |
| ISSN: | 0250-7005 |
| Popis: | Tumors express MMP-2 and MMP-9 gelatinases, which are involved in the formation of tumor vasculature. This suggests that a tumor and its surrounding neovasculature can be visualized by a sensitive gelatinase recognition method. We have studied tumor radioimaging using a gelatinase inhibitory peptide CTTHWGFTLC (CTT), which in a mouse model targets the tumor site following an intravenous injection. We determined a solution NMR structure of CTT and its retro-inversion peptide, and prepared 125I and 99mTc-labelled CTT peptide derivatives. Radiolabelled CTT inhibited gelatinases in vitro, and homed to a tumor xenograft in mice. In normal mice, CTT was instead rapidly cleared from the circulation mainly through the kidney and, after 24 h, no significant radioactivity was accumulated in healthy tissues. Gamma camera imaging of a primary tumor in live mice was obtained with double-labelled liposomes, which were coated with 99mTc-CTT and encapsulated with 125I albumin. CTT also targeted liposomes to the lungs of tumor-bearing mice, which may indicate the existence of non-visible lung micrometastases. Our studies suggest that selective gelatinase-targeting compounds could be useful in the early detection and imaging of primary tumors and metastases. |
| Databáze: | OpenAIRE |
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