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

Washington University in St. Louis, San Luis, Missouri, United States
Journal of Medicinal Chemistry (Impact Factor: 5.45). 08/2006; 49(14):4297-304. DOI: 10.1021/jm060317v
Source: PubMed


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 (111)In (T(1/2) = 2.8 d) and (86)Y (T(1/2) = 14.7 h) demonstrated. Small animal PET/CT imaging results of (86)Y-CHX-A''-octreotide in a somatostatin receptor-positive tumor-bearing rat model are presented for the validation of the novel agent.

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    • "The CHX- A " bifunctional chelator has been used successfully to radiolabel antibodies and peptides with a number of radionuclides including, 213 Bi [28] 212 Bi [29], 90 Y [30] [31], 177 Lu [32] and 111 In [31]. Recently, a novel protected version of the CHX-A " chelator was described that was suitable for solid-phase peptide synthesis [33]. A mono-N-hydroxysuccinimidyl penta-tertbutyl ester derivative of CHX-A " with a glutaric acid spacer enabled efficient coupling to peptides immobilized on solid supports or in solution. "
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