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.