DOTA-D-Tyr(1)-octreotate: a somatostatin analogue for labeling with metal and halogen radionuclides for cancer imaging and therapy.

Abstract

The goal of this study was to evaluate a somatostatin receptor ligand, DOTA-D-Tyr(1)-octreotate (DOTA-DY1-TATE), that has the chelator 1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'"-tetraacetic acid (DOTA) attached to the D-Tyr(1) residue, allowing radiolabeling with both radiohalogens and radiometals. A potential advantage of having a chelator attached to the Tyr(1) residue is that halogen radiolabels may residualize or remain trapped in tumor cells rather than clear from the tumor. DOTA-DY1-TATE was synthesized by solid-phase methods and radiolabeled with (61)Cu, (64)Cu, and (125)I in high radiochemical purity and specific activity. A competitive binding assay demonstrated that (nat)Cu-DOTA-DY1-TATE and DOTA-(nat)I-DY1-TATE had comparable affinity to (nat)In-DTPA-OC in AR42J rat pancreatic tumor cells membranes. (61)Cu-DOTA-DY1-TATE had a dissociation constant (K(d)) of 176.4 pM and a receptor concentration (B(max)) of 244.4 fmol/mg. A tumor uptake of 1.515 %ID/g was determined for (64)Cu-DOTA-DY1-TATE and 0.814 %ID/g for DOTA-(125)I-DY1-TATE in AR42J tumor bearing Lewis rats at 1 h postinjection. DOTA-(125)I-DY1-TATE remained in the tumor at a higher concentration out to 4 h postinjection, suggesting that the iodine may have residualized in the tumor cells. MicroPET imaging of (64)Cu-DOTA-DY1-TATE in AR42J tumor bearing rats and SCID mice at 2 h postinjection showed significant uptake and good contrast in the thigh tumors in the rat model and in the neck and thigh tumors of the mouse. This study demonstrates that DOTA-DY1-TATE is a somatostatin analogue that can be labeled with both metal and halogen radionuclides, and its (64)Cu- and (125)I-radiolabeled compounds showed somatostatin receptor-mediated uptake in normal and tumor tissues.

• Authors: Wen Ping Li, Jason S Lewis, Joonyoung Kim, Joseph E Bugaj, Michael A Johnson, Jack L Erion, Carolyn J Anderson
• Journal: Bioconjugate chemistry (Bioconjug Chem) 2002 Jul-Aug Vol. 13 Issue 4 Pg. 721-8 ISSN: 1043-1802 [Print] United States
• PMID: 12121126 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DOTA-Tyr(1)-octreotate
• Halogens
• Heterocyclic Compounds, 1-Ring
• Ligands
• Metals
• Peptides, Cyclic
• Radioisotopes
• Radiopharmaceuticals
• Receptors, Somatostatin
• Somatostatin
• Octreotide

Topics

• Animals
• Female
• Halogens (therapeutic use)
• Heterocyclic Compounds, 1-Ring (pharmacokinetics, therapeutic use)
• Ligands
• Male
• Metals (therapeutic use)
• Mice
• Mice, SCID
• Neoplasms (diagnostic imaging, radiotherapy)
• Octreotide (analogs & derivatives)
• Organ Specificity
• Peptides, Cyclic (pharmacokinetics, therapeutic use)
• Protein Binding
• Radioisotopes (therapeutic use)
• Radiopharmaceuticals (pharmacokinetics, therapeutic use)
• Rats
• Rats, Inbred Lew
• Receptors, Somatostatin (metabolism)
• Somatostatin (analogs & derivatives)
• Tomography, Emission-Computed
• Treatment Outcome