Imaging Somatostatin Positive Tumors with Tyr3-Octreotate/Octreotide Conjugated to Desferrioxamine B Squaramide Radiolabeled with either Zirconium-89 or Gallium-68.

Abstract

Radiolabeled derivatives of Tyr3-octreotide and Tyr3-octreotate, synthetic analogues of the peptide hormone somatostatin, can be used for positron emission tomography (PET) imaging of somatostatin receptor expression in neuroendocrine tumors. In this work, a squaramide ester derivative of desferrioxamine B (H3DFOSq) was used attach either Tyr3-octreotide or Tyr3-octreotate to the metal binding ligand to give H3DFOSq-TIDE and H3DFOSq-TATE. These new peptide-H3DFOSq conjugates form stable complexes with either of the positron-emitting radionuclides gallium-68 (t1/2 = 68 min) or zirconium-89 (t1/2 = 3.3 days). The new complexes were evaluated in an AR42J xenograft model that has endogenous expression of SSTR2. All four agents displayed good tumor uptake and produced high-quality PET images. For both radionuclides, the complexes formed with H3DFOSq-TATE performed better, with higher tumor uptake and retention than the complexes formed with H3DFOSq-TIDE. The versatile ligands presented here can be radiolabeled with either gallium-68 or zirconium-89 at room temperature. The long radioactive half-life of zirconium-89 makes distribution of pre-synthesized tracers produced to certified standards feasible and could increase the number of clinical centers that can perform diagnostic PET imaging of neuroendocrine tumors.

• Authors: Asif Noor, Jessica K Van Zuylekom, Stacey E Rudd, Peter D Roselt, Mohammad B Haskali, Eddie Yan, Michael Wheatcroft, Rodney J Hicks, Carleen Cullinane, Paul S Donnelly
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 32 Issue 7 Pg. 1192-1203 (07 21 2021) ISSN: 1520-4812 [Electronic] United States
• PMID: 33788556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gallium Radioisotopes
• Radioisotopes
• squaramide
• Somatostatin
• Gallium-68
• Quinine
• Zirconium
• Deferoxamine
• Zirconium-89
• Octreotide

Topics

• Animals
• Deferoxamine (chemistry)
• Gallium Radioisotopes (chemistry)
• Mice
• Octreotide (chemistry)
• Quinine (analogs & derivatives, chemistry)
• Radioisotopes (chemistry)
• Somatostatin (metabolism)
• Zirconium (chemistry)