title: A Phase I Dosing Study of Ferumoxytol for MR Lymphography at 3 T in Patients With Prostate Cancer.
abstract: OBJECTIVE
  The objective of our study was to determine the optimal dose of ferumoxytol for performing MR lymphography (MRL) at 3 T in patients with prostate cancer.
  
  
  METHODS
  This phase I trial enrolled patients undergoing radical prostatectomy (RP) with bilateral pelvic lymph node dissection (PLND). Three groups of five patients each (total of 15 patients) received IV ferumoxytol before RP with bilateral PLND at each of the following doses of iron: 4, 6, and 7.5 mg Fe/kg. Patients underwent abdominopelvic MRI at 3 T before and 24 hours after ferumoxytol injection using T2- and T2*-weighted sequences. Normalized signal intensity (SI) and normalized SD changes from baseline to 24 hours after injection within visible lymph nodes were calculated for each dose level. Linear mixed effects models were used to estimate the effects of dose on the percentage SI change and log-transformed SD change within visible lymph nodes to determine the optimal dose of ferumoxytol for achieving uniform low SI in normal nodes.
  
  
  RESULTS
  One patient who was excluded from the study group had a mild allergic reaction requiring treatment after approximately 2.5 mg Fe/kg ferumoxytol injection whereupon the injection was interrupted. The 15 study group patients tolerated ferumoxytol at all dose levels. The mean percentage SI change in 13 patients with no evidence of lymph metastasis was -36.4%, -45.4%, and -65.1% for 4, 6, and 7.5 mg Fe/kg doses, respectively (p = 0.041).
  
  
  CONCLUSIONS
  A dose level of 7.5 mg Fe/kg ferumoxytol was safe and effective in deenhancing benign lymph nodes. This dose therefore can be the starting point for future phase II studies regarding the efficacy of ferumoxytol for MRL.
authors.affiliation: 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Bldg 10, Rm B3B85, Bethesda, MD 20892-1088.
authors.forename: Baris
authors.initials: B
authors.lastname: Turkbey
authors.affiliation: 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Bldg 10, Rm B3B85, Bethesda, MD 20892-1088.|2 Philips Healthcare Research North America, Briarcliff Manor, NY.
authors.forename: Harsh K
authors.initials: HK
authors.lastname: Agarwal
authors.affiliation: 3 Biometric Research Branch, Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, MD.
authors.forename: Joanna
authors.initials: J
authors.lastname: Shih
authors.affiliation: 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Bldg 10, Rm B3B85, Bethesda, MD 20892-1088.
authors.forename: Marcelino
authors.initials: M
authors.lastname: Bernardo
authors.affiliation: 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Bldg 10, Rm B3B85, Bethesda, MD 20892-1088.
authors.forename: Yolanda L
authors.initials: YL
authors.lastname: McKinney
authors.affiliation: 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Bldg 10, Rm B3B85, Bethesda, MD 20892-1088.
authors.forename: Dagane
authors.initials: D
authors.lastname: Daar
authors.affiliation: 4 Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Griffiths
authors.affiliation: 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Bldg 10, Rm B3B85, Bethesda, MD 20892-1088.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sankineni
authors.affiliation: 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Bldg 10, Rm B3B85, Bethesda, MD 20892-1088.
authors.forename: Linda
authors.initials: L
authors.lastname: Johnson
authors.affiliation: 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Bldg 10, Rm B3B85, Bethesda, MD 20892-1088.
authors.forename: Kinzya B
authors.initials: KB
authors.lastname: Grant
authors.affiliation: 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Bldg 10, Rm B3B85, Bethesda, MD 20892-1088.
authors.forename: Juanita
authors.initials: J
authors.lastname: Weaver
authors.affiliation: 5 Urologic Oncology Branch, NCI, NIH, Bethesda, MD.
authors.forename: Soroush
authors.initials: S
authors.lastname: Rais-Bahrami
authors.affiliation: 6 Department of Radiology, Division of Abdominal Imaging and Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Harisinghani
authors.affiliation: 7 Cancer Imaging Program, NCI, NIH, Rockville, MD.
authors.forename: Paula
authors.initials: P
authors.lastname: Jacobs
authors.affiliation: 8 Genitourinary Malignancies Branch, NCI, NIH, Bethesda, MD.
authors.forename: William
authors.initials: W
authors.lastname: Dahut
authors.affiliation: 9 Laboratory of Pathology, NCI, NIH, Bethesda, MD.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.affiliation: 5 Urologic Oncology Branch, NCI, NIH, Bethesda, MD.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Pinto
authors.affiliation: 1 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Bldg 10, Rm B3B85, Bethesda, MD 20892-1088.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
mesh_terms: D000368:Aged; D052203:Ferrosoferric Oxide / Q000008:administration & dosage; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis / Q000473:pathology*; D008220:Lymphography / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery
chemical_list: D052203:Ferrosoferric Oxide
keywords: ferumoxytol; lymph node; metastases; prostate cancer; staging; ultrasmall superparamagnetic iron oxide (USPIO)