Magnetic resonance imaging of tumor-associated macrophages: Clinical translation

Abstract

Purpose: Tumor-associated macrophages (TAMs) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with noninvasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults. Experimental Design: In a first-in-patient, Institutional Review Board–approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (two lymphoma and three bone sarcoma) underwent pre- and postcontrast MRI. Subsequently, 20 patients (10 lymphoma and 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24 to 48 hours after i.v. injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2 relaxation times of lymphomas and bone sarcomas. Tumor T2 values of 20 patients were correlated with CD68þ and CD163þ TAM quantities on histopathology. Results: Significant ferumoxytol tumor enhancement was noted on postcontrast scans compared with precontrast scans (P ¼ 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density (P < 0.05). Within each tumor group, T2 signal enhancement on MR images correlated significantly with the density of CD68þ and CD163þ TAM (P < 0.05). Conclusions: Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies.