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

Autor: Arezou Masteri Farahani, Fariba Maleki, Nourollah Sadeghzadeh, Saeid Abediankenari, Alireza Mardanshahi
Rok vydání: 2020
Předmět:
Zdroj: Chemical Biology & Drug Design. 96:1223-1231
ISSN: 1747-0285
1747-0277
DOI: 10.1111/cbdd.13707
Popis: 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 99m 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 99m Tc-HYNIC-EPPT and 99m Tc-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 99m Tc-HYNIC-D (TPPE) was more favorable than that of 99m 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 99m Tc-HYNIC-D (TPPE) in comparison with 99m 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.
Databáze: OpenAIRE
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