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Somatostatin Receptor Subtype Specificity and in Vivo Binding of a Novel Tumor Tracer, ^99mTc-P829¹

Departments of Nuclear Medicine [I. V., M. L., C. B., T. P., D. G.], Gastroenterology [M. P-R.], Surgery [G. H.], Pathology [K. K.], and Internal Medicine I, Division of Hematology [P. V.], University of Vienna, A-1090 Vienna, Austria; Arizona Institute of Nuclear Medicine, Phoenix, Arizona 85016 [H. H.]; Department of Nuclear Medicine, National Cancer Institute, 80131 Naples, Italy [S. L., P. M.]; and Diatide, Inc., Londonderry, New Hampshire 03053 [J. L-J., R. D.]

Recent data suggest that somatostatin receptors (SSTRs) are expressed on various tumor cells. High-level expression of SSTR on the tumor cell surface provides the basis for the successful clinical use of radiolabeled ligands for the in vivo localization of tumor sites. We have characterized the in vitro binding properties of the novel SSTR ligand ^99mTc-P829 using primary human tumors (carcinoids, breast cancers, intestinal adenocarcinomas, pheochromocytomas, small cell and non-small cell lung cancer, and melanomas; n = 28), various tumor cell lines, and COS7 cells transfected with the human SSTR (hSSTR) subtypes 1, 2, 3, 4, and 5. ^99mTc-P829 bound to primary tumor cells and tumor cell lines with high affinity and high capacity. The dissociation constants (K_d) ranged between 1 and 20 nM. ^99mTc-P829 also bound with high affinity to the transfected hSSTR2 (K_d, 2.5 nM), hSSTR5 (K_d, 2 nM), and hSSTR3 (K_d, 1.5 nM). Binding of ^99mTc-P829 to hSSTR3 was found to be displaceable by unlabeled P829/([ReO]-P829), SST-14, and vasoactive intestinal peptide (VIP; IC₅₀, 2 nM) and, less effectively, by Tyr³-octreotide (IC₅₀, 20 nM). In contrast, the binding of ^99mTc-P829 to hSSTR2 and hSSTR5 could be displaced by P829/([ReO]-P829) and Tyr³-octreotide but not by VIP. ^99mTc-P829 scintigraphy revealed in vivo binding to primary or metastatic tumor sites in seven of eight patients with breast cancer and six of six patients with melanoma. In summary, our data show that ^99mTc-P829 binds with high affinity to many different types of primary and cloned tumor cells. Furthermore, our data identify hSSTR2, the VIP acceptor hSSTR3, and hSSTR5 as the respective target receptors. Because these receptors are frequently expressed at high levels on primary tumor cells, ^99mTc-P829 appears to be a promising novel peptide tracer for tumor imaging.

¹ These studies have been supported in part by the Austrian National Bank (Jubiläumsfonds Projects 5460 and 6512) and by a Foundation of the Mayor of the City of Vienna. Parts of the studies were sponsored by Diatide, Inc.

² To whom requests for reprints should be addressed, at Department of Nuclear Medicine, University of Vienna, Währinger Gürtel 18–20, A-1090 Vienna, Austria. Phone/Fax: 43-1-40400-7835; E-mail: irene.virgolini@akh-wien.ac.at.

Received 9/19/97. Accepted 3/ 3/98.

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