Radiosynthesis and Biological Evaluation of a Small-Molecule Probe for Thyroid-Stimulating Hormone Receptor

Area of Science:

• Biomedical Imaging
• Radiochemistry
• Molecular Imaging

Background:

• Thyroid-stimulating hormone receptor (TSHR) is crucial for thyroid function and its overexpression is linked to various diseases, particularly tumors.
• A novel TSHR-targeting small molecule agonist, ML-109, with nanomolar potency has been developed.

Purpose of the Study:

• To radiolabel ML-109 with iodine-131 to create the ¹³¹I-ML-109 radiotracer.
• To evaluate the biological performance of ¹³¹I-ML-109 as a single-photon emission computed tomography (SPECT) imaging probe.

Main Methods:

• Radiolabeling of ML-109 with iodine-131 on the quinazolin-4-one ring.
• Assessment of radiochemical purity and radiolabeling yield.
• Evaluation of tumor uptake in K1 and 8305C xenograft mouse models using SPECT.

Main Results:

• ¹³¹I-ML-109 was successfully synthesized with high radiochemical purity (>95%) and a moderate radiolabeling yield (∼40%).
• The radiotracer demonstrated significant tumor uptake in both K1 and 8305C xenograft models.
• ¹³¹I-ML-109 showed good biological performance as a SPECT imaging agent.

Conclusions:

• The study established a synthetic strategy for preparing ¹³¹I-ML-109.
• ML-109 serves as a promising molecular scaffold for developing TSHR-targeted imaging probes.
• Further structural optimization of ML-109 is recommended to enhance the diagnostic performance of future probes.