Abstract

BackgroundProstate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [68Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients.MethodsEligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[18F]FDG PET and/or 131I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [68Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[18F]FDG PET CT/MRI for lesion location and relative intensity.ResultsTwelve patients underwent [68Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[18F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[18F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype.Conclusions[68Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[18F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.

Highlights

  • Prostate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer

  • While Differentiated thyroid cancer (DTC) can become resistant to radioactive iodine (RAI) therapy, resistance is most commonly seen in dedifferentiated subtypes (such as poorly differentiated papillary thyroid cancer (PDPTC) and anaplastic thyroid cancer (ATC)

  • Patients were a median age of 65.5 years, and a median of 3 years from initial diagnosis at the time of [­68Ga]Ga-PSMA-11 PET/MRI. [68Ga]Ga-PSMA-11 PET/MRI was performed a median of 1.8 months from most recent 2-[18F]Fluoro‐ deoxyglucose (FDG) PET or ­[123I]Iodide/[131I]

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Summary

Introduction

Prostate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. A subset of patients with aggressive and less differentiated thyroid cancer refractory to RAI therapy succumb to their illness, with approximately 2000 deaths per year in the US [4]. For patients with disease that is not amendable to surgery and/or becomes iodine refractory (does not take up iodine in one or more lesions, or progresses despite RAI therapy [5]), treatment options are limited. The prognosis for these patients remains poor. There is an unmet clinical need for improved therapies for these patients with aggressive forms of thyroid cancer

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