Preparation and evaluation of ^99mTc‐HYNIC‐_D(TPPE) as a new targeted imaging probe for detection of colon cancer: Preclinical comparison with ^99mTc‐HYNIC‐EPPT

Abstract

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 D(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 99mTc 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 99mTc‐HYNIC‐EPPT and 99mTc‐HYNIC‐D(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 99mTc‐HYNIC‐D(TPPE) was more favorable than that of 99mTc‐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 99mTc‐HYNIC‐D(TPPE) in comparison with 99mTc‐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.

MUC1-Targeted Radiopharmaceuticals in Cancer Imaging and Therapy

“…In mice bearing HT29 xenografts, tumors were visualized 1 h after injection of 99m Tc-HYNIC- D (TPPE). These results indicated the promising features of 99m Tc-HYNIC- D (TPPE) for an in vivo targeting of MUC-1 expressing tumors . The results of radiolabeled anti-MUC1 peptides are summarized in Table .…”

“…54 For a radioisotope that is to be used for diagnosis, it must emit γ-rays with enough energy so that it can escape the body, and it should have a short enough half-life to be decayed away soon after the imaging is completed. For single photon-emission tomography (SPECT), γ-emitters with energies in the range from 100 to 250 keV are optimal and are mainly represented by 99m Tc, 123 I, and 111 In. High-energy positron-emitters such as 18 F, 68 Ga, 64 Cu, and 11 C can be used for positron-emission tomography (PET) by emitting 511 keV photons.…”

“…These results indicated the promising features of 99m Tc-HYNIC-D (TPPE) for an in vivo targeting of MUC-1 expressing tumors. 123 The results of radiolabeled anti-MUC1 peptides are summarized in Table 6.…”