Format

Send to

Choose Destination
Clin Cancer Res. 2018 Sep 1;24(17):4110-4118. doi: 10.1158/1078-0432.CCR-18-0673. Epub 2018 May 15.

Magnetic Resonance Imaging of Tumor-Associated Macrophages: Clinical Translation.

Author information

1
Department of Radiology and Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California.
2
Department of Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany.
3
Department of Pathology, Stanford Hospital, Stanford University, Stanford, California.
4
Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
5
Department of Medicine, Stanford Hospital, Stanford University, Stanford, California.
6
Department of Radiology and Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California. heiked@stanford.edu.

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 CD68+ and CD163+ TAM quantities on histopathology.Results: Significant ferumoxytol tumor enhancement was noted on postcontrast scans compared with precontrast scans (P = 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 CD68+ and CD163+ 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. Clin Cancer Res; 24(17); 4110-8. ©2018 AACR.

PMID:
29764855
PMCID:
PMC6125171
[Available on 2019-09-01]
DOI:
10.1158/1078-0432.CCR-18-0673

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center