Open AccessEvaluation of radioiodinated vesamicol analogs for sigma receptor imaging in tumor and radionuclide receptor therapy
Author(s) -
Ogawa Kazuma,
Shiba Kazuhiro,
Akhter Nasima,
Yoshimoto Mitsuyoshi,
Washiyama Kohshin,
Kinuya Seigo,
Kawai Keiichi,
Mori Hirofumi
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01279.x
Subject(s) - biodistribution , chemistry , receptor , sigma receptor , radionuclide therapy , spect imaging , kidney , ligand (biochemistry) , nuclear medicine , spleen , pharmacokinetics , radiosynthesis , pharmacology , medicine , positron emission tomography , in vitro , biochemistry
It has been reported that sigma receptors are highly expressed in a variety of human tumors. In this study, we selected (+)‐2‐[4‐(4‐iodophenyl)piperidino] cyclohexanol [(+)‐ p IV] as a sigma receptor ligand and evaluated the potential of radioiodinated (+)‐ p IV for tumor imaging and therapy. (+)‐[ 125/131 I] p IV was prepared by an iododestannylation reaction under no‐carrier‐added conditions with radiochemical purity over 99% after HPLC purification. Biodistribution experiments were performed by the intravenous injection of (+)‐[ 125 I] p IV into mice bearing human prostate tumors (DU‐145). Blocking studies were performed by intravenous injection of (+)‐[ 125 I] p IV mixed with an excess amount of unlabeled sigma ligand into DU‐145 tumor‐bearing mice. For therapeutic study, (+)‐[ 131 I] p IV was injected at a dose of 7.4 MBq followed by measurement of the tumor size. In biodistribution experiments, (+)‐[ 125 I] p IV showed high uptake and long residence in the tumor. High tumor to blood and muscle ratios were achieved because the radioactivity levels of blood and muscle were low. However, the accumulations of radioactivity in non‐target tissues, such as liver and kidney, were high. The radioactivity in the non‐target tissues slowly decreased over time. Co‐injection of (+)‐[ 125 I] p IV with an excess amount of unlabeled sigma ligand resulted in a significant decrease in the tumor/blood ratio, indicating sigma receptor‐mediated tumor uptake. In therapeutic study, tumor growth in mice treated with (+)‐[ 131 I] p IV was significantly inhibited compared to that of an untreated group. These results indicate that radioiodinated (+)‐ p IV has a high potential for sigma receptor imaging in tumor and radionuclide receptor therapy. ( Cancer Sci 2009)