Targeting aldehyde dehydrogenase: a potential approach for cell labeling.

Area of Science:

• Biomedical imaging
• Stem cell biology
• Oncology

Background:

• Developing sensitive methods for tracking stem cells is crucial for advancing stem cell therapy.
• Hematopoietic stem cells (HSCs) express aldehyde dehydrogenase-1A1 (ALDH1), a potential target for imaging and chemotherapy resistance identification.

Purpose of the Study:

• To synthesize and evaluate novel radioiodinated aldehydes as imaging agents specific for ALDH1.
• To assess the potential of these agents for tracking stem cells and identifying tumors resistant to cyclophosphamide chemotherapy.

Main Methods:

• Developed synthesis schemes for two radioiodinated aldehydes: [*I]FMIC and [*I]DEIBA.
• Evaluated the agents using purified ALDH1 enzyme and ALDH1-expressing tumor cells.

Main Results:

• Achieved good radiochemical yields for [*I]FMIC (70+/-5%) and [*I]DEIBA (47+/-14%).
• Demonstrated that ALDH1 converts both compounds to their respective acids, indicating substrate suitability.
• Failed to show specific uptake in ALDH-expressing tumor cells, despite ALDH1 activity within the cells.

Conclusions:

• The developed radioiodinated aldehydes are suitable substrates for ALDH1.
• Future radiolabeled aldehydes for ALDH1 imaging require designs that ensure sufficient polarity of reaction products for cellular retention.