Preparation and evaluation of Tc-HYNIC- (TPPE) as a new targeted imaging probe for detection of colon cancer: Preclinical comparison with Tc-HYNIC-EPPT.

The aim of this study was to prepare radiolabeled peptide-based agents for imaging of colon cancer. According to the incorporation of HYNIC for radiolabeling with technetium-99m, two analogs were designed and compared: an antitumor-antibody-derived peptide based on the EPPT sequence and a novel retro-inverso peptidomimetic derivative (TPPE) structurally modified by replacing the L-amino acids with D-amino acids and reversing the primary amino acid sequence of EPPT. The HYNIC-conjugated peptides were labeled with Tc using tricine/EDDA coligand with more than 98% radiochemical yield and showed high metabolic stability. Kd values of 41.77 ± 7.34 nM and 37.33 ± 8.37 nM for Tc-HYNIC-EPPT and Tc-HYNIC- (TPPE) confirmed high affinity of both peptides for cell surface antigen MUC1. These radiotracers demonstrated no significant differences in the cellular uptake and internalization value, but the biodistribution profile of Tc-HYNIC- (TPPE) was more favorable than that of Tc-HYNIC-EPPT as a result of better tumor-to-non-target ratios for the examined tissues and organs. HT29 tumors were visualized more clearly in scintigraphic images with Tc-HYNIC- (TPPE) in comparison with Tc-HYNIC-EPPT. The results showed the retro-inverso analog to be a more promising radiotracer as a probe for in vivo targeting of HT-29 tumors than the parent peptide.