⁶⁸Ga-DOTA-RGD₂ Positron Emission Tomography/Computed Tomography in Radioiodine Refractory Thyroid Cancer: Prospective Comparison of Diagnostic Accuracy with ¹⁸F-FDG Positron Emission Tomography/Computed Tomography and Evaluation Toward Potential Theranostics

Background: Radioiodine therapy (¹³¹I) forms a principal cornerstone in the management of differentiated thyroid cancer. Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) presents a challenge in detection of structural disease in patients with evidence of biochemical disease and in treatment of the disease using alternate therapies. The present study was conducted to compare the diagnostic accuracy (in terms of sensitivity and specificity) of ⁶⁸Ga-DOTA-RGD₂ positron emission tomography (PET)/computed tomography (CT) as a neoangiogenesis imaging modality with ¹⁸F-FDG PET/CT, the current standard in diagnostic algorithm of RAIR-DTC, and to evaluate the radiotracer avidity on ⁶⁸Ga-DOTA-RGD₂ PET/CT for potential theranostics. Methods: Forty-four RAIR-DTC patients with negative post-Therapy ¹³¹I scan were prospectively enrolled. Serum thyroglobulin (sTg) and anti-Thyroglobulin (ATg) measurements were performed with levothyroxine withdrawal (thyrotropin-stimulated state), and ¹⁸F-FDG PET/CT and ⁶⁸Ga-DOTA-RGD₂ PET/CT studies were performed within 1 week of each other. Follow-up was performed with histopathology/sTg/ATg/conventional imaging. The findings of ¹⁸F-FDG PET/CT and ⁶⁸Ga-DOTA-RGD₂ PET/CT were compared with the reference standard to obtain sensitivity, specificity, and overall accuracy. Degree of radiotracer uptake on ⁶⁸Ga-DOTA-RGD₂ PET/CT was described as tumor to background (T/B) and tumor to liver (T/L) ratios of standardized uptake value. Results: ⁶⁸Ga-DOTA-RGD₂ PET/CT detected a total of 123 lesions, with an overall sensitivity, specificity, and accuracy of 82.3%, 100%, and 86.4%, respectively. ¹⁸F-FDG PET/CT detected a total of 144 lesions, with an overall sensitivity, specificity, and accuracy of 82.3%, 50%, and 75%, respectively. Most commonly identified disease sites were nodal metastases (82.9%), followed by thyroid bed lesions (10.5%). 82.1% of patients positive on ⁶⁸Ga-DOTA-RGD₂ PET/CT showed lesional radiotracer uptake higher than the liver (grade IV and grade V). Conclusions: ⁶⁸Ga-DOTA-RGD₂ PET/CT showed a similar sensitivity to, but higher specificity and overall accuracy than ¹⁸F-FDG PET/CT in detection of lesions in RAIR-DTC patients. This novel application of the angiogenesis imaging modality can prove useful in RAIR-DTC, especially in patients with negative/suspicious ¹⁸F-FDG PET/CT. Furthermore, since the majority of patients (82.1%) positive on ⁶⁸Ga-DOTA-RGD₂ PET/CT showed radiotracer avidity toward the higher end of the spectrum (grade IV and grade V), novel ¹⁷⁷Lu-based theranostics can be a potential treatment for these patients.