99mTc-HYNIC-D4 Peptide: A New Small Radiolabeled Peptide for Non Small Cell Lung Tumor Targeting.

Abstract

The aim of this study was to evaluate the 99mTc-HYNIC-D4 peptide as a new radiotracer for tumor targeting in non small cell lung tumor that overexpresses epidermal growth factor receptor (EGFR). D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as a candidate for specific targeting on EGFR. It was conjugated with HYNIC on N-terminus and labeled with 99mTc using tricine as a co-ligand. The cellular and animal studies were evaluated for specific binding of this labeled peptide. Radiochemical purity was determined to be 98% by instant thin layer chromatography and reverse-phase high performance liquid chromatography. Stability of radiolabeled peptide was more than 90% up to 24 h incubation in solution at 37 oC. Specific binding of the radiolabeled peptide to the EGFR showed dissociation constant of 181 ± 41 nM. Animal biodistribution in normal and A-549 xenografted nude mice showed rapid clearance from blood and other non target organs. Tumor uptake values as %ID/g (percentage of injection dose per gram of tissue) were 8.07% at 1 h and 3.82% at 4 h after injection that was blocked by presaturation of EGFR using an excess of cold peptide. This study showed that 99mTc-HYNIC-D4 is a promising tumor targeting radiotracer on the non small cell lung tumor.