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Validation of a Novel CHX-A‘ ‘ Derivative Suitable for Peptide Conjugation:  Small Animal PET/CT Imaging Using Yttrium-86-CHX-A‘ ‘-Octreotide

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journal contribution
posted on 2006-07-13, 00:00 authored by Thomas Clifford, C. Andrew Boswell, Gráinne B. Biddlecombe, Jason S. Lewis, Martin W. Brechbiel
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 111In (T1/2 = 2.8 d) and 86Y (T1/2 = 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.

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