Development of a Novel ^99mTc-Labeled Folate Derivative Containing Phenyl Isonitrile to Target Folate Receptor with...

Area of Science:

• Radiopharmaceutical chemistry
• Molecular imaging
• Oncology

Background:

• Folate receptors are highly expressed in tumors, making them attractive targets for imaging agents.
• Existing folate-based imaging agents suffer from high kidney uptake, limiting their clinical utility.
• Developing new tracers with improved biodistribution profiles is crucial for effective cancer diagnosis.

Purpose of the Study:

• To design and synthesize a novel folate-based imaging agent with reduced renal accumulation.
• To evaluate the efficacy of the new agent, [[99mTc]Tc-(CNMBFA)6]+, for folate receptor-targeted tumor imaging.
• To assess the safety and diagnostic potential of the developed radiotracer.

Main Methods:

• A phenyl-isonitrile folate derivative (CNMBFA) was synthesized and labeled with technetium-99m using a one-step kit.
• In vitro studies assessed labeling yield, stability, hydrophilicity, cell uptake, and receptor specificity.
• In vivo studies in tumor-bearing mice evaluated biodistribution, tumor targeting, and renal uptake using micro-SPECT/CT imaging.

Main Results:

• The radiolabeling achieved a high yield (>95%) with excellent in vitro stability and hydrophilicity.
• The complex [[99mTc]Tc-(CNMBFA)6]+ demonstrated specific binding to folate receptors.
• In vivo studies showed significant tumor uptake and notably lower renal accumulation compared to previous tracers.

Conclusions:

• The novel technetium-99m labeled folate derivative, [[99mTc]Tc-(CNMBFA)6]+, is a specific folate receptor-targeting agent.
• This agent exhibits favorable biodistribution with reduced renal uptake, making it a promising candidate for tumor imaging.
• The developed radiotracer offers potential for improved cancer diagnosis with minimized radiation exposure to the kidneys.