Synthesis and biological evaluation of Tc-99m-cyclopentadienyltricarbonyltechnetium-labeled octreotide.

Octreotide was labeled at its N-terminus with Tc-99m-cyclopentadienyltricarbonyltechnetium, and the biodistribution of the labeled conjugate was studied in adult female Sprague-Dawley rats. The synthesis began with the preparation of Tc-99m-(methoxycarbonylcyclopentadienyl) tricarbonyltechnetium from Tc-99m-pertechnetate using a novel double ligand transfer reaction; it was completed in a total of five steps, with an 8% overall radiochemical yield (15% decay-corrected). The 99mTc-cyclopentadienyltricarbonyltechnetium-labeled octreotide conjugate (99mTc-CpTT-octreotide) showed receptor-mediated uptake in the pancreas and adrenals, which was blocked (80% and 93%, respectively) by excess unlabeled octreotide. These studies illustrate a new method for labeling a peptide with Tc-99m through an organometallic linkage that is stable, nonpolar, and low molecular weight; it complements labeling approaches that utilize inorganic metal complexes.