DRUG ELUTING MICROSPHERES

CHARACTERISTICS OF AVAILABLE AGENTS

RAJ NARAYANAN M.D.

PROFESSOR OF CLINICAL RADIOLOGY

CHIEF – VASCULAR & INTERVENTIONAL RADIOLOGY

UNIVERSITY OF MIAMI – MILLER SCHOOL OF MEDICINE

Govindarajan Narayanan, M.D.

•Consulting: BTG/Angiodynamics

Drug eluting Microspheres

LC Bead/LUMI

Hepasphere

Tandem

Off label use

ADVANTAGES OF MICROSPHERES

DEB vs. conventional TACE Pharmacokinetics: serum concentration over time

* From Varela et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: Efficacy and doxorubicin pharmacokinetics. J

Hepatology 46 (2007) 474-481

Commonly loaded drugs

Doxorubicin

Irinotecan

BEAD SIZES LC Beads

500-700 & 300-500

300-500 & 100-300

100-300

M1

Tandem

40, 75, 100µm

Quadrasphere

30-60

50-100

100-150

150-200

PREPARATION

TANDEM

TANDEM

POLYZENE F SHELL

Biocompatible

HYDROGEL CORE

Felxible

Hydrophilic

Crosslinked Methacrylate polymer

TANDEM KEY FEATURES

Loads faster

Can load upto 50mg/ml – 150 mg in one 3ml vial

Slower release

Copolymer of vinyl acetate and

methyl acrylate

Non degradable, hydrophilic material

Dry size 50-100µ expands to 200-400µ;

30-60µ expands to 120-240µ in

saline/non-ionic contrast

QuadraSphere Microspheres (US name)

HepaSphere Microspheres (ROW)

Microspheres are not PVA

based

Unique formulation results in

a highly compressible sphere

that moulds to the vessel

lumen and architecture

Achieves complete occlusion

and increased intimal contact,

even in bifurcated vessels

QuadraSphere / HepaSphere Microspheres

Courtesy of Dr. K. Osuga

Doxorubicin is loaded by

two processes:

1. Mechanical absorption

2. Ionic interaction

Negatively charged polymer bonds with positively

charged doxorubicin*

-O O

OH

O O-

OH

n

O

OH

C

O

NH3+

OH

H3C

OCH3 O

O OH

OH

O

CH2OH

HepaSphere Microspheres:

Doxorubicin loading and delivery

Doxorubicin loads throughout spheres for

controlled release

Contact with vessel intima enhances occlusion

and doxorubicin delivery

Photos courtesy of Dr. Gupta

TREATMENT WITH QUADRASPHERE

50 YEAR OLD MALE

HISTORY OF HCC HCC

SINGLE TREATMENT WITH 2 VIALS OF QUADRASHERE

2 VIALS 30-60 MICRON SIZE LOADED WITH 50 MG OF DOXORUBICIN

DELIVERY SIZE 120-240 MICRONS

PRE TREATMENT CT

PRE AND POST HEPASHPERE

4 WEEKS POST TREATMENT CT

LC BEAD

Soft deformable microspheres

Reduce blood flow to tumor

Slow release of Drug enhances the

anti-tumor effect and decreases

systemic exposure

The LC Bead has a negative charge and

doxorubicin has a positive charge

The doxorubicin is loaded and eluted by an

‘reversible ionic exchange mechanism’.

Hydrated Beads Loaded Beads

Interaction of doxorubicin with

SO3 groups displaces water from

the hydration shells

Hydration shell

associated with

PVA and ionic groups

Bulk (non-

bound)

water

Relative Drug Distributions

LC BEAD CASE EXAMPLE

TACE WITH DOXO BEADS

FOLLOW UP CT

RADIOOPAQUE LCBEAD-LUMI

Provide intraprocedural feedback with visualization under fluoroscopy (2D) and

CBCT (3D) to aid in targeted embolization

Discover regions at risk for under- treatment; may improve outcomes

Radiopaque LC Bead®: LUMI

Kindly provided by Drs. Duran, Lin, and Geschwind.

Data on file, Biocompatibles UK Ltd, a BTG International group company.

CBCTWithout Soluble Contrast

CASE EXAMPLE - Pretreatment Dyna CT

30

CT, computed tomography.

Post-treatment Dyna CT

31

THANK