Molecular Targeting and Imaging of Non-Functional Pituitary Tumors : Preliminary Results

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Our goal is to determine the molecular pathogenesis of pituitary tumors. We have identified new molecular targets and have developed a novel molecular-targeted imaging agent for non-functional pituitary adenomas. Tumor specimens from surgery were used in these studies. Microarray analyses, RT-qPCR, Western blotting analysis, immunochemistry and folate-binding studies were performed to determine folate receptor expression. Primary cell culture, folate-PEG-liposome uptake, folate-PEG-liposome-DOX (doxorubicin) uptake and cytotoxicity studies were performed. In vivo imaging was performed by injection of FolateScan followed by planar and SPECT/CT imaging in patients with clinically non-functional pituitary tumors prior to pituitary surgery. All the analyses indicated that the folate-receptor was significantly and uniquely upregulated in non-functional pituitary adenomas. Folate-PEG-liposomes carrying the antineoplastic drug doxorubicin induced cell-death in folate-receptor α expressing pituitary tumors in vitro, as measured by MTT assays. Using a folate-receptor targeted technetium-99 labeled radionuclide imaging molecule imaged, FolateScan successfully folate-receptor expressing tumors. Non-folate-receptor expressing tumors were not imaged by FolateScan. Folate-receptor positive and negative tumors were validated by Western blotting analysis. These preliminary results support the concept of FolateScan as a novel diagnostic imaging tool for clinically non-functional tumors, and folate receptor targeted therapy as a medical treatment for these tumors, options which currently do not exist.
日本脳神経外科コングレスの論文
2006-06-20

Molecular Targeting and Imaging of Non-Functional Pituitary Tumors : Preliminary Results

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