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)