Somatostatin receptor subtype specificity and in viva binding of a novel tumor tracer, 99mTc-P829

Irene Virgolini, Maria Leimer, Hirsch Handmaker, Secondo Lastoria, Claudia Bischof, Pietro Muto, Thomas Pangerl, Doris Gludovacz, Markus Peck-Radosavljevic, John Lister-James, Gerhard Hamilton, Klaus Kaserer, Peter Valent, Richard Dean

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1850-1859
Number of pages10
JournalCancer Research
Volume58
Issue number9
Publication statusPublished - May 1 1998

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Somatostatin Receptors
Neoplasms
Octreotide
Tumor Cell Line
Inhibitory Concentration 50
Melanoma
Breast Neoplasms
Ligands
Vasoactive Intestinal Peptide
Carcinoid Tumor
Pheochromocytoma
Non-Small Cell Lung Carcinoma
Radionuclide Imaging
Adenocarcinoma
Peptides

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Virgolini, I., Leimer, M., Handmaker, H., Lastoria, S., Bischof, C., Muto, P., ... Dean, R. (1998). Somatostatin receptor subtype specificity and in viva binding of a novel tumor tracer, 99mTc-P829. Cancer Research, 58(9), 1850-1859.

Somatostatin receptor subtype specificity and in viva binding of a novel tumor tracer, 99mTc-P829. / Virgolini, Irene; Leimer, Maria; Handmaker, Hirsch; Lastoria, Secondo; Bischof, Claudia; Muto, Pietro; Pangerl, Thomas; Gludovacz, Doris; Peck-Radosavljevic, Markus; Lister-James, John; Hamilton, Gerhard; Kaserer, Klaus; Valent, Peter; Dean, Richard.

In: Cancer Research, Vol. 58, No. 9, 01.05.1998, p. 1850-1859.

Research output: Contribution to journalArticle

Virgolini, I, Leimer, M, Handmaker, H, Lastoria, S, Bischof, C, Muto, P, Pangerl, T, Gludovacz, D, Peck-Radosavljevic, M, Lister-James, J, Hamilton, G, Kaserer, K, Valent, P & Dean, R 1998, 'Somatostatin receptor subtype specificity and in viva binding of a novel tumor tracer, 99mTc-P829', Cancer Research, vol. 58, no. 9, pp. 1850-1859.
Virgolini I, Leimer M, Handmaker H, Lastoria S, Bischof C, Muto P et al. Somatostatin receptor subtype specificity and in viva binding of a novel tumor tracer, 99mTc-P829. Cancer Research. 1998 May 1;58(9):1850-1859.
Virgolini, Irene ; Leimer, Maria ; Handmaker, Hirsch ; Lastoria, Secondo ; Bischof, Claudia ; Muto, Pietro ; Pangerl, Thomas ; Gludovacz, Doris ; Peck-Radosavljevic, Markus ; Lister-James, John ; Hamilton, Gerhard ; Kaserer, Klaus ; Valent, Peter ; Dean, Richard. / Somatostatin receptor subtype specificity and in viva binding of a novel tumor tracer, 99mTc-P829. In: Cancer Research. 1998 ; Vol. 58, No. 9. pp. 1850-1859.
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AU - Bischof, Claudia

AU - Muto, Pietro

AU - Pangerl, Thomas

AU - Gludovacz, Doris

AU - Peck-Radosavljevic, Markus

AU - Lister-James, John

AU - Hamilton, Gerhard

AU - Kaserer, Klaus

AU - Valent, Peter

AU - Dean, Richard

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N2 - 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.

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