Design, characterization and evaluation of a new ^99mTc-labeled folate derivative with affinity towards folate...

Area of Science:

• Nuclear medicine
• Radiopharmaceutical chemistry
• Oncology

Background:

• Folate receptors (FRs) are over-expressed in various human cancers, making them a key target for diagnostic imaging.
• Radiolabeled folate derivatives offer a non-invasive method for tumor detection and treatment planning.

Purpose of the Study:

• To synthesize and evaluate a novel 99mTc-labeled radiotracer for targeting folate receptors in cancer imaging.
• To assess the binding affinity, specificity, and in vivo performance of the new radiotracer.

Main Methods:

• Synthesis of a 99mTc-labeled folate derivative using 99mTc-'4+1' chemistry.
• Confirmation of radiochemical purity (>95%) via radio-HPLC and structural analysis of a rhenium analogue.
• In vitro evaluation using folate receptor-positive (KB) and negative (A549) cell lines.
• In vivo studies in KB tumor xenograft models.

Main Results:

• The 99mTc-complex achieved >95% radiochemical purity.
• The ligand showed weaker affinity to FRs than folic acid (IC50 8.09 µM vs 29.46 nM).
• The 99mTc-labeled complex demonstrated high specificity (~90%) for FR-positive KB cells and moderate in vivo tumor uptake (~2.6% at 3h) with high specificity (~80%).

Conclusions:

• The synthesized 99mTc-labeled folate derivative exhibits promising specificity for folate receptor-positive cancer cells.
• The observed in vitro and in vivo characteristics support further investigation of this molecular probe for improved cancer imaging applications.