Comparison of 99mTc octreotide‐tetramine conjugates with in vitro and in vivo affinity for the somatostatin receptor

Abstract

AbstractGiven that many cancer cells overexpress somatostatin (SMS) receptors on their membrane, several SMS analogs labeled with radionuclides have been developed aiming at the scintigraphic diagnosis and/or radiotherapy of SMS‐positive neoplasms. Thus, a synthetic analog of the peptide hormone somatostatin (SMS) labeled with 111In (OctreoScan® 111) is routinely used for the in vivo localization of SMS‐positive tumors in the clinic. Given that 99mTc remains the gold standard in Diagnostic Nuclear Medicine, we have synthesized two metabolically stabilized SMS analogs, N4‐Bzl‐Glyc‐Tyr3‐octreotide, 1, and N4‐Bzl‐Suc‐octreotide, 2, by covalent coupling of a N4 bifunctional ligand to the N‐terminal of the peptide backbone. The two analogs can be easily labeled with 99mTc under mild conditions leading to a single radiolabeled product in high yields and high specific activities. Both analogs significantly retain their ability to bind to the SMS receptor, as shown by proper competition binding experiments. After their administration in healthy mice both radiolabeled analogs were rapidly excreted from the body into the urine through the kidneys. The accumulation of the radioactivity in the SMS receptor rich organs, like pancreas and adrenals, was found specific by in vivo blocking tests.