Magnetic Resonance Imaging of Tumor-Associated Macrophages: Clinical Translation

Abstract

<b>Purpose:</b> 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.<b>Experimental Design:</b> In a <i>first-in-patient</i>, 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 CD68⁺ and CD163⁺ TAM quantities on histopathology.<b>Results:</b> Significant ferumoxytol tumor enhancement was noted on postcontrast scans compared with precontrast scans (<i>P</i> = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density (<i>P</i> < 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68⁺ and CD163⁺ TAM (<i>P</i> < 0.05).<b>Conclusions:</b> 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. <i>Clin Cancer Res; 24(17); 4110-8. ©2018 AACR</i>.