Analysis Determines Potential Feasibility of PSMA PET Imaging for Metastatic Thyroid Cancer

Courtney Lawhn-Heath, MD

Gallium-68 prostate-specific membrane antigen ([⁶⁸Ga]Ga-PSMA-11) PET imaging demonstrated the ability to detect metastatic thyroid cancer but resulted in a lower detection rate compared with 2-[¹⁸F]FDG PET for thyroid cancer lesion visualization, suggesting the thyroid cancer subtype on its own may not be sufficient to predict PSMA uptake, according to findings from a feasibility study.¹

The prospective pilot study, led by Courtney Lawhn-Heath, MD, of the University of California San Francisco, aimed to determine the feasibility, as well as the utility, of [⁶⁸Ga]Ga-PSMA-11 PET/MRI in patients with thyroid cancer. Adult patients with a history of pathology-driven thyroid cancer and an abnormal radiotracer uptake on recent FDG to be included in the study, and they then underwent the PSMA PET for comparison in terms of lesion location and relative intensity.²

Patients with thyroid cancer often exhibit favorable responses to surgery and risk-adapted postoperative therapy with thyroid hormone suppression and radioactive iodine (RAI) therapy, but there remains a subset of patients with more aggressive and less differentiated disease that can be resistant to RAI therapy. These patients typically have poor outcomes and limited treatment options, marking this an area of unmet clinical need.

PSMA-targeting therapies have demonstrated promise in prostate cancer, more recently obtaining approval of [⁶⁸Ga]Ga-PSMA-11 as the first PSMA radiotracer approved in December 2020. However, expression of PSMA is not specific to men with prostate cancer, which led to the rationale for exploring [⁶⁸Ga]Ga-PSMA-11 in thyroid cancer.

A total of 11 patients underwent the PSMA PET and were included in the study, of which 7 had differentiated thyroid cancer (DTC), including 2 papillary thyroid cancers (PTCs), 2 follicular thyroid cancers (FTCs), and 2 Hurthle cell carcinoma; 4 patients had dedifferentiated thyroid cancer, including 2 with poorly differentiated PTC (PDPTC) and 2 with anaplastic thyroid cancer (ATC). There were 43 lesions across all 11 patients, including 33 in DTC and 11 in dedifferentiated subtypes.¹

The median age of patients with 65.5 years (range, 47-80), and the median time from initial diagnosis to PSMA PET was 3 years (range, 0-28). The median time from the most recent FDG PET to PSMA PET was 1.8 months (range, 0.4-11.4), and 9 patients underwent PSMA PET within 3 months of their most recent imaging. No patients had received any new treatments or treatment changes between imaging, and all patients had metastatic disease.

Overall, 8 of 11 patients had positive disease on PSMA PET compared with 9 of 11 with FDG PET. Among 43 lesions, 41 were visually FDG positive with a detection rate of 95.3%, and 28 lesions were PSMA positive with a detection rate of 65.1% The 2 FDG negative lesions were PSMA positive in a patient with FTC. The median SUVmax was substantially lower for lung lesions compared with other locations, at 4.2 (range, 2.5-19.1) for FDG PET and 2.6 for PSMA PET (range, 1.2-4.5), and the highest was observed in extrapulmonary soft tissue metastases at a median of 14.2 (range, 3.5-31.4) and 15.8 (range, 6.2-27.7), respectively.

The detection rate for the DTC cohort was 93.8% for FDG PET compared with 53.1% for PSMA PET, and the median lesion SUVmax was 9.0 for FDG PET (range, 3.5-28.4) and 9.2 for PSMA PET (range, 2.0-27.8). The detection rate for the dedifferentiated cohort was 100% for FDG PET compared with 72.7% for PSMA PET, and the median SUVmax was 8.0 days (range, 2.6-19.1) and 5.1 for PSMA PET (range, 1.6-12.6), respectively. The detection rate for PSMA PET was highest for FTC and PDPTC (80.0%, each), but the numbers of patients in each of these groups were limited.

Tumor radiotracer uptake was heterogeneous within the cancer subtypes, as well as within individual patients. In some patients, only the FDG PET was able to detect a small right middle lobe metastasis. The investigators made note of the other patient with PDPTC who did not demonstrate a higher median lesion SUVmax on PSMA PET at 4.5 compared with FDG PET at 5.3. A patient with FTC had higher median lesion SUVmax on PSMA PET at 15.0 compared with FDG PET at 3.5. A right fourth rib metastasis was also observed on PSMA PET but not on FDG PET. The other patient with FYC had higher PSMA than FDG uptake in 2 metastases but substantially lower PSMA uptake than FDG in a T10 metastasis; the PSMA SUVmax was 7.4 and FDG SUVmax 18.3.

Eight of 11 patients had lesion FDG uptake higher than the PSMA uptake, but lesions were still considered positive on PSMA PET in 5 of the 8 patients.

“PSMA PET offered an advantage in visualization of intracranial metastases due to the lack of background brain uptake compared to FDG,” Lawhn-Heath et al wrote. “However, multiple extracranial metastatic lesions in the same patient were better seen on FDG. In addition, evidence of molecular heterogeneity was noted in some individual tumors.”

No adverse events were reported in this analysis.

“The exploration of PSMA PET as a possible theranostic agent in thyroid cancer is in its infancy. The use of PSMA radioligand therapy in DTC is beginning to be explored, but there are currently no accepted guidelines to determine the eligibility for PSMA RLT in thyroid cancer,” Lawhn-Heath et al concluded.

_References

_{1. Lawhn-Heath C, Yom SS, Liu C, et al. Gallium-68 prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) PET for imaging of thyroid cancer: a feasibility study. EJNMMI Res. 2020. 10:128. doi: 10.1186/s13550-020-00720-3}

_{2. The Exploration of PSMA PET as a Possible Theranostic Agent in Thyroid Cancer. Press Release. January 11, 2021. Accessed January 14, 2021. https://bit.ly/3qlTX9D}