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Mechanism of Action Combidex in MR Imaging. Mukesh Harisinghani, MD Department of Radiology, Massachusetts General Hospital. Overview. Current limitations for LN staging in cancer Combidex enhanced MRI Mechanism of action

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mechanism of action combidex in mr imaging
Mechanism of Action Combidex in MR Imaging

Mukesh Harisinghani, MD

Department of Radiology,

Massachusetts General Hospital

overview
Overview
  • Current limitations for LN staging in cancer
  • Combidex enhanced MRI
    • Mechanism of action
    • Fulfills unmet clinical need of staging LN in patientswith known primary cancer
why image lymph nodes
Why Image Lymph Nodes?
  • Accurate staging of the primary cancerAppropriate treatment
    • Prostate Cancer
      • LN Positive  Treatment changed to non-surgical
  • Get a sense of the prognosis
    • Bladder Cancer
      • Node Negative  10-year survival 57–87%
      • Node Positive  5-year survival 35–38%

Risk of death increases 20% with each additional + LN

Cheville et al. Cancer 97, 2003.

current ln staging
Current LN Staging
  • Non-Invasive
    • Imaging
  • Invasive
    • Surgical LN Sampling (gold standard)
slide5

Size Criteria

< 10 mm

Benign

< 8 mm

> 10 mm

Malignant

> 8 mm

slide6

Benign

Malignant

Size criterion is inaccurate

18 mm in short axis

5 mm in short axis

morphology central necrosis
Morphology – Central Necrosis
  • CT in Cervical Cancer
  • Positive predictive valueof 100% for nodal metastases
  • Most necrotic nodes haddiameter > 2 cm

Yang et al. AJR 2000;175.

pelvic lymphadenectomy
Pelvic Lymphadenectomy
  • Pelvic lymph node dissection (PLND) accompanied by frozen section pathological examination
  • Standard pelvic lymphadenectomyis limited
  • Extended pelvic lymphadenectomy
    • Incidence of lymph node metastases increased from 10% to 26.2%

Heidenreich et al. J Urol. April 2002.

slide10

Extended lymph node dissection

    • Obturator nerve injury
    • Trauma to major vessels

Narayan et al. Urology 1994;44:519–24.

  • Frozen section pathologic analysis has false negative rate of 30–40%
  • Young et al. J Clin Path 52,1999.
current need
Current Need
  • Non-invasive technique that detects andcharacterizes LN with high degreeof sensitivity and specificity
  • Broad anatomic coverage for all LN
slide12

Combidex

(ferumoxtran-10)

Nanoparticles

Size: 21 nm

R1: 17 mMsec-1

R2: 48 mMsec-1

slide13

Combidex

(ferumoxtran-10)

Uptake by normal lymph nodes

technique
Technique
  • 1.5 T MR systems using pelvic phasearray coil (Siemens Magnetom, GE Horizon)
  • Imaging time/sequences (25 minutes/patient)
    • T2 FSE sequences
    • T2* gradient echo sequences
    • 3D gradient echo sequences
  • Post-processing
    • 3D reconstruction
slide15

24 hours

Post-contrast

Pre-contrast

slide19

Unenhanced MR

Combidex enhanced MR

clinical impact
Clinical Impact
  • Improved clinical staging
  • Surgical planning
  • Radiation therapy planning
  • Image-guided intervention
slide21

COMBIDEX®

(ferumoxtran-10)