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

Radiolabeled derivatives of Tyr(3)-octreotide and Tyr(3)-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 (H(3)DFOSq) was used attach either Tyr(3)-octreotide or Tyr(3)-octreotate to the metal binding ligand to give H(3)DFOSq-TIDE and H(3)DFOSq-TATE. These new peptide-H(3)DFOSq 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 H(3)DFOSq-TATE performed better, with higher tumor uptake and retention than the complexes formed with H(3)DFOSq-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.

Automated summary

In this study, new peptide-H(3)DFOSq conjugates were used for PET imaging of neuroendocrine tumors, showing good tumor uptake and high-quality images, with H(3)DFOSq-TATE performing better than H(3)DFOSq-TIDE. The long half-life of zirconium-89 makes it a promising positron-emitting radionuclide that may increase the availability of diagnostic PET imaging for neuroendocrine tumors in clinical settings.