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 <i>N</i>-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-<i>N</i>-hydroxysuccinimidyl penta-<i>tert</i>-butyl ester derivative of CHX-A‘ ‘ (<i>trans</i>-cyclohexyldiethylenetriaminepenta-acetic acid) featuring a glutaric acid spacer. Commercially obtained octreotide was modified at its <i>N</i>-terminus by this reagent in the solution phase, and its subsequent radiolabeling with ¹¹¹In (<i>T</i>_1/2 = 2.8 d) and ⁸⁶Y (<i>T</i>_1/2 = 14.7 h) demonstrated. Small animal PET/CT imaging results of ⁸⁶Y-CHX-A‘ ‘-octreotide in a somatostatin receptor-positive tumor-bearing rat model are presented for the validation of the novel agent.