Novel positron emission tomography tracer distinguishes normal from cancerous cells

Area of Science:

• Oncology
• Biomedical Imaging
• Molecular Biology

Background:

• Positron emission tomography (PET) probes are crucial for cancer diagnosis, staging, and treatment monitoring.
• Thymidylate synthase (TSase) is a key enzyme in DNA synthesis and a target for cancer drug development.
• Rapidly dividing cancer cells exhibit increased TSase activity, utilizing (R)-N(5),N(10)-methylene-5,6,7,8-tetrahydrofolate (MTHF) as a cofactor.

Purpose of the Study:

• To evaluate the potential of radiolabeled MTHF as a substrate for identifying rapidly dividing cancer cells.
• To investigate the uptake of [(14)C]MTHF in various cancer and normal cell lines.
• To establish proof-of-principle for [(11)C]MTHF as a novel PET imaging tracer.

Main Methods:

• Cancerous (MCF7, MDA-MB-231, hTERT-HME1) and normal (human mammary epithelial, MCF10A, HT-29, FHC) cell lines were incubated with [(14)C]MTHF.
• Radiotracer uptake was measured after incubation periods ranging from 30 minutes to 2 hours.
• Factors influencing MTHF uptake, including cell doubling time, folate receptor status, S phase percentage, and TSase expression, were analyzed.

Main Results:

• Cancer cell lines demonstrated significantly higher [(14)C]MTHF incorporation compared to their normal counterparts.
• MTHF uptake correlated with cell doubling time, folate receptor status, S phase percentage, and TSase expression.
• These findings indicate differential MTHF metabolism between cancerous and normal cells.

Conclusions:

• [(14)C]MTHF uptake can distinguish between cancerous and normal cells.
• The study supports the potential of [(11)C]MTHF as a novel PET tracer for cancer imaging.
• Further research is warranted to validate [(11)C]MTHF for clinical applications in oncology.