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

• Published in: Bioconjugate chemistry Vol. 32; no. 7; pp. 1192 - 1203
• Main Authors: Noor, Asif, Van Zuylekom, Jessica K, Rudd, Stacey E, Roselt, Peter D, Haskali, Mohammad B, Yan, Eddie, Wheatcroft, Michael, Hicks, Rodney J, Cullinane, Carleen, Donnelly, Paul S
• Format: Journal Article
• Language: English
• Published: Washington American Chemical Society 21-07-2021
• Subjects: Deferoxamine; Gallium; Gallium isotopes; Half-life; Image quality; Ligands; Medical imaging; Neuroendocrine tumors; Octreotide; Peptides; Positron emission; Positron emission tomography; Radioactive half-life; Radioisotopes; Room temperature; Somatostatin; Somatostatin receptors; Tomography; Tumors; Xenografts; Xenotransplantation; Zirconium; Zirconium isotopes
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.1c00109

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 (t 1/2 = 68 min) or zirconium-89 (t 1/2 = 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.