Tracking Cell Transplants in Femoral Osteonecrosis with Magnetic Resonance Imaging: A Proof-of-Concept Study in Patients.

Ashok J Theruvath, Hossein Nejadnik, Anne M Muehe, Felix Gassert, Norman J Lacayo, Stuart B Goodman, Heike E Daldrup-Link

Journal: Clinical cancer research : an official journal of the American Association for Cancer Research 2019;24(24):6223-6229

PMID: 30224340

Abstract

PURPOSE

Osteonecrosis is a devastating complication of high-dose corticosteroid therapy in patients with cancer. Core decompression for prevention of bone collapse has been recently combined with the delivery of autologous concentrated bone marrow aspirates. The purpose of our study was to develop an imaging test for the detection of transplanted bone marrow cells in osteonecrosis lesions.

EXPERIMENTAL DESIGN

In a prospective proof-of-concept clinical trial (NCT02893293), we performed serial MRI studies of nine hip joints of 7 patients with osteonecrosis before and after core decompression. Twenty-four to 48 hours prior to the surgery, we injected ferumoxytol nanoparticles intravenously to label cells in normal bone marrow with iron oxides. During the surgery, iron-labeled bone marrow cells were aspirated from the iliac crest, concentrated, and then injected into the decompression track. Following surgery, patients received follow-up MRI up to 6 months after bone marrow cell transplantation.

RESULTS

Iron-labeled cells could be detected in the access canal by a dark (negative) signal on T2-weighted MR images. T2* relaxation times of iron-labeled cell transplants were significantly lower compared with unlabeled cell transplants of control patients who were not injected with ferumoxytol ( = 0.02). Clinical outcomes of patients who received ferumoxytol-labeled or unlabeled cell transplants were not significantly different ( = 1), suggesting that the added ferumoxytol administration did not negatively affect bone repair.

CONCLUSIONS

This immediately clinically applicable imaging test could become a powerful new tool to monitor the effect of therapeutic cells on bone repair outcomes after corticosteroid-induced osteonecrosis.

©2018 American Association for Cancer Research.

Address: Department of Radiology, Pediatric Radiology, Lucile Packard Children's Hospital, Stanford University, Stanford, California.; Department of Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany.; Pediatric Molecular Imaging Program, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California.; Department of Pediatrics, Pediatric Hematology/Oncology, Lucile Packard Children's Hospital and Stanford Cancer Center, Stanford University, Stanford, California.; Department of Orthopaedic Surgery and Bioengineering, Stanford Hospital, Stanford University, Stanford, California.; Department of Radiology, Pediatric Radiology, Lucile Packard Children's Hospital, Stanford University, Stanford, California. [email protected].
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