Imaging Somatostatin Positive Tumors with Tyr 3 -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.