Download - Radioactive Stents

Klaus Schloesser, Forschungszentrum Karlsruhe, Technik und Umwelt /HZY

Radioactive Stents

Production and History

Klaus Schloesser, Forschungszentrum Karlsruhe / HZY

Stent Stent

remodeling

neointima

Plaque [mm2]

Comparison of IVUS data Average data of 157 radioactive und 140 non radioactive stents


„Edge Effekt“


In early days

• 1991 Fischell: US-Patent: Radioactive Stent

• 1992 Hehrlein, Heidelbergwanted radioactive Stents -> animal trials

• 1994 Liermann, Frankfurt

Treatment of peripheral arteries (legs) 192Ir – Afterloader

• 1995 Connado, Venezuela192Ir – Afterloader (manuel)


Radioactive Stent in Rabbits

• 55Co... left

• 32Pright


Methods of Activation


Radioisotope• 1 day < halflife < 3 Weeks

• Suitable radiation for Brachytherapy with stents

Range about 2-5 mm -radiation of low energy - radiation of high energy

– no -radiation(does not reach target volume, too much damage in the vicinity)

– No deeply penetration -radiation (health physics problems)


Phosphorous -32


Heavy Ion Implantation

Depth distribution of implanted P-32

0%

5%

10%

15%

20%

25%

0 20 40 60 80 100 120

Depth [nm]

conc

entr

atio

n [a

rbitr

ary

units

]


Ion Source

Acceleration

Mass separation

Target

M=31 M=32


ECRIS – magnetic bottle

mc

eBmr

m

PLTTT cyccyclincyc

;;

22

22

)sin(0 tEeE x

x

yz

2.45GHz)( 87,5mTGHz][0357,0]T[ ffB


ECRIS-radial Confinement by Hexapole

N

S

S

NS

N

N

S N

S

S

Nx

yz


Precursor of Plasma is Gas• Red Phosphorous sublimates at about 440°C (ugh !)

gaseous compound: PH3 (Phosphine)

• Phosphine is very poisonous– MAK = 0,1 ml/m³ = 1/10 threshold for smelling (Garlik)

• Radio toxicity – Inhalation von 1 m³ Air (32P/31P) = 1/1000 results in effective

dose > 5 Sv which corresponds to LD50 (ugh , really!)

– So, let’s make only that much Phosphine at a time, so that the ion source is just filled. (0,5l at 10-4mbar)

• H• + P PH• or. H+ + P PH+ etc. up to PH3


ECRIS – with two stage extraction and plasma chamber made of glass

100

M

30 kV

60 kV


Overview of ion implanter


Mass Spectrum

16O231PH

28SID214N2D212C16O

D232P


Ion source

acceleration

separation

target

M=31 M=32

Irradiation chamber


Irradiation


Irradiation platform


Discharge behaviour

ca. 3 h


Performance of the ion source for 32PEfficiency Ca. 20% in main beam

Time for discharge 3 hours, almost no mixture of fresh with old Phosphorous

Emittance (beam spot size)

beam < 2 mm at a vertical deflection > 20 mm

Maintenances After 1 year Extraction was exchanged due to HV-problems

Stability Unattended operation over night is no problem


Quality control: Measurement of activity distribution


Special activity distributions

Lot # M.5023-000502R SN-1, pass,

-2000

-1500

-1000

-500

0

500

1000

1500

2000

0 20 40 60 80 100 120 140

channel w idth = .301 mm

Coun

ts/c

hann

el


Quality control: encapsulation of activity

• Test method: washing of stents in isotonic sodiumchlorid (0,9% NaCl) in an ultrasonic bath

cumulative washout

0

0,2

0,4

0,6

0,8

1

1,2

1,4

0 200 400

time [minutes]

w [

% o

f to

tal a

ctiv

ity]

15 min used in routine quality control

washout constant after two hours < 0.1%/ hour


How much activity (how many ions) fits on a stent?

Wash off versus implanted ion dose for perpendicular and oblique incidence of beam

0

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

2

1,E+13 1,E+14 1,E+15 1,E+16 1,E+17 1,E+18

ions / sqcm

wash

out

[% o

f tot

al a

ctiv

ity]

90°

30°

> 30°

< 30°


If „drug – eluting“ works, prevention of restenosis with

radioactive stents is not the first choice

• perspectives– e.g. oncology

dose application within 2mm distancebut restricted to target volume