The clinical signification and application value of [⁶⁸Ga]Ga-PSMA imaging in thyroid malignancy

Approximately 5% of differentiated thyroid cancers lose the ability to uptake iodine, leading to limited treatment options and poor prognosis due to invasion and distant metastasis. PSMA imaging probes have been proposed as a potential diagnostic and therapeutic tool for iodine-refractory thyroid cancer. However, there are limited reports and significant heterogeneity in patient selection, warranting further exploration of the application value of PSMA in thyroid cancer.

We performed Western Blot, PCR, and [⁶⁸Ga]Ga-PSMA uptake experiments on cell lines and conducted in vivo small animal imaging. Clinical and radiological results of included differentiated thyroid cancer patients were collected. (Trial registration number: 2021-669, Trial registration date: December 30, 2021).

PSMA expression levels were significantly higher in poorly differentiated thyroid cancer (7.86 ± 1.90 vs. 1.00 ± 0, P < 0.01; 7.86 ± 1.90 vs. 0.03 ± 0.02, P < 0.01), but [⁶⁸Ga]Ga-PSMA imaging correlated with tumor burden, such as 18F-FDG (8.08 ± 7.74 and 5.67 ± 4.23, P = 0.01) and Tg levels (307.1 ± 183.4 vs. 118.0 ± 116.1, P = 0.002).

Our results showed that PSMA expression increased with the decrease of thyroid cancer differentiation. However, the level of [⁶⁸Ga]Ga-PSMA uptake in thyroid cancer patients was not significantly associated with the degree of thyroid cancer differentiation, but also with the metabolism and burden of tumors such as 2-[¹⁸F]FDG and Tg levels. These findings provide additional clinical significance and application value for PSMA in thyroid cancer.