Mechanism of Action Combidex in MR Imaging Mukesh Harisinghani, MD Department of Radiology, Massachusetts General Hospital.

Mechanism of Action Combidex in MR Imaging

Mukesh Harisinghani, MD

Department of Radiology,

Massachusetts General Hospital

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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

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Why Image Lymph Nodes?

Accurate staging of the primary cancer

Appropriate 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.

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Current LN Staging

Non-InvasiveNon-Invasive

ImagingImaging

InvasiveInvasive

Surgical LN Sampling (gold standard)Surgical LN Sampling (gold standard)

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Size Criteria

< 10 mm< 10 mm

< 8 mm< 8 mm

BenignBenign

> 10 mm> 10 mm

> 8 mm> 8 mm

MalignantMalignant

BenignBenign MalignantMalignant

18 mm in short axis 5 mm in short axis

Size criterion is inaccurateSize criterion is inaccurate

Morphology – Fatty Hilum

MalignantMalignantBenignBenign

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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.

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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.

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.

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Current Need

Non-invasive techniqueNon-invasive technique that detects andcharacterizes LN with high degreeof sensitivity and specificity

Broad anatomic coverageBroad anatomic coverage for all LN

Combidex(ferumoxtran-10)

NanoparticlesSize: 21 nmR1: 17 mMsec-1R2: 48 mMsec-1

Uptake by normal lymph nodes

Combidex(ferumoxtran-10)

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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

Pre-contrastPre-contrast Post-contrastPost-contrast

24 hours

20 mm20 mm

Unenhanced MRUnenhanced MR Combidex enhanced MRCombidex enhanced MR

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Clinical Impact

Improved clinical staging

Surgical planning

Radiation therapy planning

Image-guided intervention

COMBIDEX®COMBIDEX®

(ferumoxtran-10)(ferumoxtran-10)