Integrin α_vβ₃ Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using ^99mTc-3PRGD2

Abstract

Integrin a v b 3 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 a v b 3 imaging in the detection of RAIR DTC lesions using 99m Tc-PEG 4 -E [PEG 4 -c(RGDfK)] 2 ( 99m Tc-3PRGD2), thus providing a feasible antiangiogenetic therapeutic target. Methods: Ten DTC patients (2 men, 8 women; mean age 6 SD, 56.4 6 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 131 I whole-body scan (WBS) results. Clinical data were collected including history, 131 I WBS, 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 99m Tc-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 99m Tc-3PRGD2 SPECT images. There was a significant correlation between the mean tumor-to-background ratios and mean growth rates of target lesions (r 5 0.878, P 5 0.009). Conclusion: The RAIR ( 131 I WBS-negative/thyroglobulin-positive) metastatic lesions can be traced using 99m Tc-3PRGD2 imaging, meaning these lesions are highly neovascularized. 99m Tc-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.

99mTc-3PRGD2 SPECT to monitor early response to neoadjuvant chemotherapy in stage II and III breast cancer

“…Targeting integrin αvβ3 overexpressed on tumor vasculature, 99m Tc-3PRGD 2 has shown high tumor accumulation in many types of malignant lesions [14][15][16][17]26]. Moreover, it has been shown that 99m Tc-3PRGD 2 uptake is positively correlated with the integrin α v β 3 expression level.…”

Novel “Add-On” Molecule Based on Evans Blue Confers Superior Pharmacokinetics and Transforms Drugs to Theranostic Agents

“…As a proof of concept, we conjugated NMEB and DMEB to c(RGDfK), hereafter referred to as arginine-glycine-aspartic acid (RGD) peptide, for targeting cell surface receptor integrin a v b 3 . This integrin receptor is overexpressed in various malignancies and has a crucial role in tumor angiogenesis (7)(8)(9). We demonstrated that either NMEB-RGD or DMEB-RGD could be of use as an imaging agent and as a radiotherapeutic agent for the treatment of integrin a v b 3 -expressing tumors.…”

TERT Promoter Mutation Predicts Radioiodine-Refractory Character in Distant Metastatic Differentiated Thyroid Cancer

“…Early identification of non-radioiodine avidity would be helpful in avoiding unnecessary radioiodine therapy and allowing for timely adjustment to a subsequent feasible therapy. In a previous study, we used 99m Tc-3PRGD2 imaging targeting integrin a v b 3 to trace radioiodinerefractory metastatic lesions; active angiogenesis in rapidly growing radioiodine-refractory foci could be detected (4). In another study, we found that the B-Raf proto-oncogene (BRAF) V600E mutation was associated with non-radioiodine avidity in distant metastatic DTC (5), implying that molecular characteristics may drive the early identification of non-radioiodine avidity.…”