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

Clin Cancer Res. 2018 Dec 15;24(24):6223-6229. doi: 10.1158/1078-0432.CCR-18-1687. Epub 2018 Sep 17.

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 (P = 0.02). Clinical outcomes of patients who received ferumoxytol-labeled or unlabeled cell transplants were not significantly different (P = 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Bone Marrow Transplantation* / methods
  • Bone Regeneration
  • Cell Tracking* / methods
  • Female
  • Femur Head Necrosis / diagnostic imaging*
  • Femur Head Necrosis / etiology
  • Femur Head Necrosis / therapy*
  • Ferrosoferric Oxide / chemistry
  • Humans
  • Magnetic Resonance Imaging* / methods
  • Magnetite Nanoparticles / chemistry
  • Male
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Proof of Concept Study
  • Staining and Labeling
  • Treatment Outcome
  • Young Adult

Substances

  • Magnetite Nanoparticles
  • Ferrosoferric Oxide

Associated data

  • ClinicalTrials.gov/NCT02893293