Molecular Imaging of Galectin-1 Expression as a Biomarker of Papillary Thyroid Cancer by Using Peptide-Functionalized Imaging Probes

Abstract

Thyroid cancers are the most frequent endocrine cancers and their incidence is increasing worldwide. Thyroid nodules occur in over 19–68% of the population, but only 7–15% of them are diagnosed as malignant. Diagnosis relies on a fine needle aspiration biopsy, which is often inconclusive and about 90% of thyroidectomies are performed for benign lesions. Galectin-1 has been proposed as a confident biomarker for the discrimination of malignant from benign nodules. We previously identified by phage display two peptides (P1 and P7) targeting galectin-1, with the goal of developing imaging probes for non-invasive diagnosis of thyroid cancer. The peptides were coupled to ultra-small superparamagnetic particles of iron oxide (USPIO) or to a near-infrared dye (CF770) for non-invasive detection of galectin-1 expression in a mouse model of papillary thyroid cancer (PTC, as the most frequent one) by magnetic resonance imaging and fluorescence lifetime imaging. The imaging probes functionalized with the two peptides presented comparable image enhancement characteristics. However, those coupled to P7 were more favorable, and showed decreased retention by the liver and spleen (known for their galectin-1 expression) and high sensitivity (75%) and specificity (100%) of PTC detection, which confirm the aptitude of this peptide to discriminate human malignant from benign nodules (80% sensitivity, 100% specificity) previously observed by immunohistochemistry.

Galectin-1 From Cancer-Associated Fibroblasts Promotes the Invasion and Metastasis of Gastric Cancer Through TGF-β1-Induced Epithelial-Mesenchymal Transition

“…GAL-1 has been found in multiple tumor cells, including melanoma, lung cancer [30], pancreatic cancer [31], bladder cancer [32], thyroid cancer [33], cervical cancer [34], and colorectal cancer [35]. In the present study, we showed that the GAL-1 protein and LGALS1 mRNA levels in GC tissue were signi cantly higher than those in NGCT, suggesting that GAL-1/LGALS1 is associated with the malignant biological behavior of GC.…”

New biomarkers: prospect for diagnosis and monitoring of thyroid disease

“…They identified the peptide (P7) that explicitly targeted galectin-1 by phage display and coupled it to imaging probes, such as near-infrared dye (CF770) or ultra-small superparamagnetic particles of iron oxide (USPIO), for non-invasive detection of galectin-1 expression in PTC by fluorescence or magnetic resonance imaging. The peptidefunctionalized imaging probe showed an exceptional specificity (100%) and a high sensitivity (75%) of PTC detection, confirming the ability of this peptide to discriminate between malignant and benign TNs (159). Galectin-3, a carbohydrate-binding protein involved in tumor progression and metastasis (160), has also been investigated as a PTC tissue marker due to its specificity in the differential diagnosis of thyroid cancer (161,162).…”

Fibroblastic galectin-1-fostered invasion and metastasis are mediated by TGF-β1-induced epithelial-mesenchymal transition in gastric cancer

“…GAL-1 has been found in multiple tumor cells, including melanoma, lung cancer [ 31 ], pancreatic cancer [ 32 ], bladder cancer [ 33 ], thyroid cancer [ 34 ], cervical cancer [ 35 ], and colorectal cancer [ 36 ]. The results of the present study demonstrated that the GAL-1 protein and LGALS1 mRNA levels in GC tissue were significantly higher than those in NGCT, suggesting that GAL-1/ LGALS1 is associated with the malignant biological behavior of GC.…”