MRI detection of breast cancer micrometastases with a fibronectin-targeting contrast agent

Abstract

Metastasis is the primary cause of death in breast cancer patients. Early detection of high-risk breast cancer, including micrometastasis, is critical in tailoring appropriate and effective interventional therapies. Increased fibronectin expression, a hallmark of epithelial-to-mesenchymal transition, is associated with high-risk breast cancer and metastasis. We have previously developed a penta-peptide CREKA (Cys-Arg-Glu-Lys-Ala)-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agent, CREKA-Tris(Gd-DOTA)3 (Gd-DOTA (4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecyl gadolinium), which binds to fibrin–fibronectin complexes that are abundant in the tumour microenvironment of fast-growing breast cancer. Here we assess the capability of CREKA-Tris(Gd-DOTA)3 to detect micrometastasis with MRI in co-registration with high-resolution fluorescence cryo-imaging in female mice bearing metastatic 4T1 breast tumours. We find that CREKA-Tris(Gd-DOTA)3 provides robust contrast enhancement in the metastatic tumours and enables the detection of micrometastases of size <0.5 mm, extending the detection limit of the current clinical imaging modalities. These results demonstrate that molecular MRI with CREKA-Tris(Gd-DOTA)3 may facilitate early detection of high-risk breast cancer and micrometastasis in the clinic.

A retrospective study of pattern of recurrence after radical surgery for thoracic esophageal carcinoma with or without postoperative radiotherapy

“…Prenzel et al (31) found that 15% of patients with pT1N0M0 carcinoma of the esophagus and even those with submucosal infiltration show nodal micrometastasis. Methods should be used to early discovery the removed or unremoved micrometastasis (32,33). Lymphatic recurrence was the most common pattern for patients without PRT, 87.9% in the present study.…”

Mutational profiles of breast cancer metastases from a rapid autopsy series reveal multiple evolutionary trajectories

“…Assessing every metastatic tumor would be ideal, particularly in light of recent findings of hormone therapy-resistant mutations in ER (ESR1 gene) found in only one or a subset of metastatic tumors within a given patient (6,7). Unfortunately, sampling every metastasis is currently impossible in a living patient, and very small tumors (<2 mm) and micrometastases are not readily detectable by current imaging techniques (8). Samples from rapid autopsy series present a unique opportunity to study the biogenesis and progression of tumor metastasis.…”

Contrast‑enhanced magnetic resonance imaging with a novel nano‑size contrast agent for the clinical diagnosis of patients with lung cancer

“…A previous study has indicated that MRI contrast agent was able to detect an early stage glioma (39). In addition, fibronectin-targeting contrast agent in combination with MRI may detect breast cancer micrometastases (40). The present study revealed that BsAbCENS, when used with MRI, significantly improved the diagnostic accuracy and sensitivity for patients with lung cancer.…”