1999 Fiscal Year Final Research Report Summary
Development of novel radiopharmaceuticals for diagnostic imaging of sigma receptors in human brain and non-invasive visualization of sigma receptor positive tumors
| Project/Area Number |
09670963
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Osaka University of Pharmaceutical Sciences |
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Principal Investigator |
OHMOMO Yoshiro Osaka University of Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (70183241)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Sigma Receptor / Radiopharmaceutical / SPECT / Tumor Imaging / Iodine-125 / Iodine-123 |
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| Research Abstract |
Sigma receptors have been the focus of intense study because of their potential to offer new insights into the mechanism of psychoses, movement disorders, and neurodegeneration. Recently, high densities of sigma receptors have been demonstrated in several tumor-derived cell lines.
SPECT and PET radiopharmaceuticals specific for sigma receptors would be of great value as diagnostic tools for movement disorders and certain psychotic illness, and for non-invasive visualization of sigma receptor expressed tumors in vivo.
In the present research, novel radioiodinated ligands were designed based on structure-activity relationship, synthesized and characterized. Among the newly synthesized compounds, both 125-I labeled 2-BON and 3-BON {1-(2 and 3- [125-I]iodophenylpropyl)-4-(3,4-dimethoxybenzyl)piperazine} were found to possess very high affinity and selectivity for sigma receptors. Biodistribution studies of these two radioligands in mice and rats showed rapid brain uptake and specific brain accumulation consistent with sigma receptor density in vivo. Especially, 125-I labeled 2-BON visualized sigma receptors in rat brain very clearly using autoradiography.
125-I labeled 2-BON also showed very high affinity and specificity for the sigma receptors expressed on tumor cells and revealed that A-375 tumor cells had 10 times more sigma receptors than the rat brain.
These results suggest that 125-I labeled 2-BON, in its I-123 labeled form, could serve as a promising radiopharmaceutical to image sigma receptors in human brain and to visualize non-invasively sigma receptor positive tumors in vivo using SPECT.
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