title: [111In-DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: synthesis, radiolabeling and in vitro validation.
abstract: Somatostatin receptor-positive human tumors can be detected using radioiodinated analogues of somatostatin, both in vitro and in vivo. [123I-Tyr3]-octreotide has been successfully used in the visualization of somatostatin receptor-positive tumors by gamma camera scintigraphy, but this radiopharmaceutical has some major drawbacks, which can be overcome with other radionuclides such as 111In. As starting material for a potentially convenient radiopharmaceutical, a diethylenetriaminopentaacetic acid (DTPA) conjugated derivative of octreotide (SMS 201-995) was prepared. This peptide, [DTPA-D-Phe1]-octreotide (SDZ 215-811) binds more than 95% of added 111In in an easy, single-step labeling procedure without necessity of further purification. The specific somatostatin-like biologic effect of these analogues was proven by the inhibition of growth hormone secretion by cultured rat pituitary cells in a dose-dependent fashion by octreotide, [DTPA-D-Phe1]-octreotide and non-radioactive [115In-DTPA-D-Phe1]-octreotide. The binding of [111In-DTPA-D-Phe1]-octreotide to rat brain cortex membranes proved to be displaced similarly by natural somatostatin as well as by octreotide, suggesting specific binding of [111In-DTPA-D-Phe1]-octreotide to somatostatin receptors. The binding of the indium-labeled compound showed a somewhat lower affinity when compared with the iodinated [Tyr3]-octreotide, but indium-labeled [DTPA-D-Phe1]-octreotide still binds with nanomolar affinity. In conjunction with in vivo studies, these results suggest that [111In-DTPA-D-Phe1]-octreotide is a promising radiopharmaceutical for scintigraphic imaging of somatostatin receptor-positive tumors.
authors.affiliation: Department of Nuclear Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands.
authors.forename: W H
authors.initials: WH
authors.lastname: Bakker
authors.forename: R
authors.initials: R
authors.lastname: Albert
authors.forename: C
authors.initials: C
authors.lastname: Bruns
authors.forename: W A
authors.initials: WA
authors.lastname: Breeman
authors.forename: L J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: P
authors.initials: P
authors.lastname: Marbach
authors.forename: J
authors.initials: J
authors.lastname: Pless
authors.forename: D
authors.initials: D
authors.lastname: Pralet
authors.forename: B
authors.initials: B
authors.lastname: Stolz
authors.forename: J W
authors.initials: JW
authors.lastname: Koper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000000981:diagnostic imaging; D015282:Octreotide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000032:analysis*; D017481:Receptors, Somatostatin
chemical_list: D007205:Indium Radioisotopes; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; C071632:SDZ 215-811; D004369:Pentetic Acid; D015282:Octreotide