posted on 2006-07-13, 00:00authored byThomas 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.