[111In-DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: synthesis, radiolabeling and in vitro validation

Life Sci. 1991;49(22):1583-91. doi: 10.1016/0024-3205(91)90052-d.

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Female
  • In Vitro Techniques
  • Indium Radioisotopes
  • Isotope Labeling
  • Molecular Sequence Data
  • Neoplasms / diagnostic imaging
  • Octreotide / analogs & derivatives*
  • Octreotide / chemical synthesis
  • Octreotide / metabolism
  • Octreotide / pharmacology
  • Pentetic Acid / analogs & derivatives*
  • Pentetic Acid / chemical synthesis
  • Pentetic Acid / metabolism
  • Pentetic Acid / pharmacology
  • Pituitary Gland, Anterior / drug effects
  • Radioligand Assay
  • Radionuclide Imaging
  • Rats
  • Receptors, Neurotransmitter / analysis*
  • Receptors, Somatostatin

Substances

  • Indium Radioisotopes
  • Receptors, Neurotransmitter
  • Receptors, Somatostatin
  • SDZ 215-811
  • Pentetic Acid
  • Octreotide