Prostate-Specific Membrane Antigen in Anaplastic and Poorly Differentiated Thyroid Cancer—A New Diagnostic and Therapeutic Target?

Abstract

Several studies have demonstrated an expression of the prostate-specific membrane antigen (PSMA) in the cancer-related neovasculature of thyroid malignancies. Due to the poor prognosis and limited therapeutic options for patients with anaplastic (ATC) and poorly differentiated (PDTC) thyroid carcinoma, the aim of our study was to investigate the theranostic approach of PSMA expression in these patients. The PSMA uptake on Gallium-68 (68Ga)-PSMA-positron emission tomography/computed tomography (PET/CT) and glucose uptake on F-18-Fluordeoxyglucose (18F-FDG)-PET/CTs were analysed in two ATC and six PDTC patients. The PSMA expression in corresponding patients’ tissue samples was detected by immunohistochemistry. In addition, various tissue sections from 22 ATC and six PDTC patients were examined concerning PSMA expression. 68Ga-PSMA-PET/CT showed heterogeneous PSMA expression among patients and lesions. Six of the eight analyzed patients (two ATC, four PDTC) showed increased glucose metabolism without increased PSMA uptake after PET/CT. In one patient (PDTC), 18F-FDG-PET/CT tracer uptake was positive and 68Ga-PSMA-PET/CT showed heterogeneous results. Another patient (PDTC) evidenced only PSMA-positive lesions and received two cycles of Lutetium-177 (177Lu)-PSMA therapy, which kept his disease stable for seven months. There was a correlation between immunohistochemical PSMA expression and uptake on 68Ga-PMSA-PET/CT in three of the examined patients. Twenty-seven of the analyzed 39 ATC and 13 of the analyzed 22 PDTC tissue sections showed a strong PSMA expression. Considering the rarity of PDTC and ATC, which is the reason for the small patient population we studied, the findings of this study confirm the high diagnostic sensitivity and superiority of 18F-FDG-PET/CT in comparison to 68Ga-PSMA-PET/CT in the diagnosis of ATC and PDTC. However, it can be suggested that 68Ga-PMSA-PET/CT can be considered as a beneficial adjunct to the well-established 18F-FDG-PET/CT for a few individual selected patients with ATC and PDTC to detect lesions not discovered by 18F-FDG-PET/CT and to determine patients’ eligibility for a radioligand therapy. Radiolabelled PSMA-ligands may, in the future, represent a theranostic approach with only minor side effects for a few individual selected patients with ATC and PDTC who need alternative treatment options in case of progression when established therapies are no longer effective. However, due to the small sample size of our collective, larger studies are needed to allow for a final evaluation on the significance of PSMA-targeted diagnostic and therapy for ATC and PDTC.

PSMA Expression in Solid Tumors beyond the Prostate Gland: Ready for Theranostic Applications?

“…Moreover, from the comparative analyses, it emerged that the PSMA expression was higher in the primary tumors than metastatic sites due to their different microenvironments and signalling pathways. Furthermore, 7 out of 8 patients who underwent both 18 F-FDG PET/CT and 68 GaPSMA PET/CT showed higher FDG uptake rates compared to PSMA uptake, showing that 18 F-FDG-PET/CT still has higher accuracy than 68 Ga-PSMA PET/CT in detecting more aggressive thyroid cancer histotypes [ 20 ]. On the other hand, de Vries et al retrospectively analyzed a small cohort of 5 patients affected by radioiodine-refractory thyroid cancer by using the dual-tracer approach ( 18 F-FDG and 68 Ga-PSMA PET/CT).…”

“…In particular, the 68 Ga-PSMA PET/CT performed 5 weeks after the second cycle showed size decreases in several lung lesions, response of the liver metastases and stable disease of the cervical metastases [ 21 ]. Finally, Wächter et al reported one PDTC patient who received two cycles of 177 Lu-PSMA therapy, based on high PSMA uptake based on PSMA PET/CT and 18 F-FDG-negative scans, with a time interval of 8 weeks (cumulative dose 13.7 GBq), showing stable disease for 7 months, followed by an increase in Tg levels and the appearance of 18 F-FDG-positive metastases [ 20 ].…”

Advanced imaging and theranostics in thyroid cancer

“…Theranostics are of particular interest for such aggressive cancers, but are challenging to evaluate in such rare malignancies; clinically available radiotracers have been used in few patients on an experimental basis. Ga68-PSMA PET/CT and MRI were recently performed among a small cohorts of patients with PDTC and ATC [95,96], with variable results: 74% of poorly differentiated tumor metastases were detected in one small study, while only 11% of PDTC metastases (and no ATC metastases) were detected in another. In the latter study, only one patient underwent treatment with Lu-177 PSMA, stabilizing their disease for 7 months [96].…”

“…Ga68-PSMA PET/CT and MRI were recently performed among a small cohorts of patients with PDTC and ATC [95,96], with variable results: 74% of poorly differentiated tumor metastases were detected in one small study, while only 11% of PDTC metastases (and no ATC metastases) were detected in another. In the latter study, only one patient underwent treatment with Lu-177 PSMA, stabilizing their disease for 7 months [96].…”

PET-CT in Clinical Adult Oncology—V. Head and Neck and Neuro Oncology

“…It should be noted that differentiated and undifferentiated thyroid cancer can be positive on PSMA-targeting PET-CT that is done for prostate cancer [ 85 ]. This may support a future theranostic target in patients with treatment-refractory DTC or anaplastic thyroid cancer [ 86 ]. Incidental focal uptake of either FDG or a PSMA-ligand in the thyroid or in cervical nodes in a patient with prior thyroid cancer should prompt additional evaluation.…”