Validation of a novel CHX-A" derivative suitable for peptide conjugation:: Small animal PET/CT imaging using yttrium-86-CHX-A"-octreotide

A versatile bifunctional chelating reagent based on a preorganized cyclohexyl derivative of DTPA (CHX-A ") has been developed for the convenient N-terminal labeling of peptides with metal ion radionuclides of Bi(III), In(III), Lu(III), or Y(III). This was achieved via the synthesis of a mono-N-hydroxysuccinimidyl penta-tert-butyl ester derivative of CHX-A" (trans-cyclohexyldiethylenetriaminepenta-acetic acid) featuring a glutaric acid spacer. Commercially obtained octreotide was modified at its N-terminus by this reagent in the solution phase, and its subsequent radiolabeling with In-111 (T-1/2 = 2.8 d) and Y-86 (T-1/2 = 14.7 h) demonstrated. Small animal PET/CT imaging results of Y-86-CHX-A"-octreotide in a somatostatin receptor-positive tumor-bearing rat model are presented for the validation of the novel agent.