Integrin αvβ3 imaging of radioactive iodine-refractory thyroid cancer using 99mTc-3PRGD2

Abstract

Integrin αvβ3 has been proposed as a potential imaging target for radiolabeled RGD peptides and a molecular marker for the estimation of tumor angiogenesis, yet it has not been applied in differentiated thyroid cancer (DTC) patients with radioactive iodine-refractory (RAIR) lesions. The current study was conducted to assess the potential of integrin αvβ3 imaging in the detection of RAIR DTC lesions using 99mTc-PEG4-E [PEG4-c(RGDfK)] 2 (99mTc-3PRGD2), thus providing a feasible antiangiogenetic therapeutic target. Methods: Ten DTC patients (2 men, 8 women; mean age ± SD, 56.4 ± 9.8 y; age range, 42-73 y) with multiple RAIR metastases were recruited; all patients had both elevated thyroglobulin levels (thyroglobulin-positive) and negative 131I whole-body scan (WBS) results. Clinical data were collected including history, 131IWBS, contemporary CT, ultrasonography, thyroid-stimulating hormone, thyroglobulin, and antithyroglobulin. One or 2 target lesions were selected on the contemporary CT images using Response Evaluation Criteria in Solid Tumors 1.0 for all patients, 7 of whom were chosen for the calculation of the rates of lesion growth within the 3 mo before the study. WBS at 30 min and regional SPECT for lesions at 1 h were performed after the intravenous injection of 99mTc-3PRGD2. Two experienced nuclear medicine physicians read the images in a masked fashion. The tumor-to-background ratios were calculated for further analysis. Results: All the target RAIR metastatic lesions were identified as positive on 99mTc-3PRGD2 SPECT images. There was a significant correlation between the mean tumor-to-background ratios and mean growth rates of target lesions (r = 0.878, P = 0.009). Conclusion: The RAIR (131I WBS-negative/thyroglobulin-positive) metastatic lesions can be traced using 99mTc-3PRGD2 imaging, meaning these lesions are highly neovascularized. 99mTc-3PRGD2 angiogenesis imaging can be used for the localization and growth evaluation of RAIR lesions, providing a new therapeutic target and a novel imaging modality to monitor the efficacy of certain antiangiogenetic therapy. COPYRIGHT © 2012 by the Society of Nuclear Medicine and Molecular Imaging, Inc.