Tumor pretargeting in mice using (99m)Tc-labeled morpholino, a DNA analog

Area of Science:

• Bioconjugation Chemistry
• Molecular Imaging
• Cancer Research

Background:

• Traditional tumor pretargeting strategies using streptavidin-biotin or avidin-biotin face challenges like endogenous biotin interference and immunogenicity.
• Development of alternative pretargeting agents is crucial for improving tumor localization and imaging accuracy.

Purpose of the Study:

• To evaluate the efficacy of morpholino (MORF) oligomers as a novel pretargeting agent for tumor localization.
• To assess the biodistribution and tumor uptake of a MORF-based pretargeting system in a preclinical mouse model.

Main Methods:

• Conjugation of an anti-carcinoembryonic antigen antibody with a MORF oligomer and a complementary MORF (cMORF) with a radiolabeling moiety (99mTc-MAG3).
• Evaluation of the biodistribution of 99mTc-MAG3-cMORF in normal mice and in tumor-bearing mice after antibody pretargeting.
• Comparison of radioactivity levels in tumors and normal organs between pretargeted and control groups.

Main Results:

• 99mTc-MAG3-cMORF showed rapid renal excretion in normal mice, with low whole-body retention at 3 hours.
• In tumor-bearing mice, pretargeting resulted in significant tumor uptake (2 %ID/g) at 24 hours, with minimal uptake in other organs.
• Control animals (without antibody pretargeting) exhibited substantially lower tumor uptake (0.05 %ID/g).

Conclusions:

• Morpholino oligomers represent a viable alternative for pretargeting applications in tumor localization.
• MORF-based pretargeting effectively targets tumors while minimizing off-target accumulation in a preclinical setting.