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

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.