LDR: Source DesignAAPM

2005 Summer SchoolSeattle University

18-July-2005

Robert E. Wallace, Ph.D.Samuel Oschin Comprehensive Cancer Institute

Cedars-Sinai Medical CenterLos Angeles, CA

LDR Definition & RationaleBell (1903) first published suggestion to implant tumors with encapsulated isotope to capitalize on advantages in localized dose distribution=> Benefits: spare early & late responding tissueShortened Tx duration overcomes re-populationLDR reduces late effects more than local control

Leads to: Encapsulation and contents, radiation type, half-life, energy, and activity selected for low-dose rates and local penetration / conformal distribution.

LDR History - IsotopesEarly 20th century: sealed sources of radiumMid-century: man-made isotopes in wires and/or discrete encapsulated sources: 182Ta, 192Ir, 137Cs, 198Au, 60Co, 125I, 169Yb, 32P, 103Pd, and 252CfMost recent design development driven by prostate implant procedures using 125I and 103Pd leading to many source designs from many manufacturersRenewed interest (1965 2004) isotope application:

131Cs seeds for permanent prostate implants

LDR History – Implant SystemsBefore computers were placement rules, dose tables, and dose specification criteria for particular plane and volume geometries.Manchester (Paterson & Parker, 1934, 38)Quimby (1944) UniformParis (Pierquin, et al. 1978) 192Ir wires / strandsParker sought uniform dose in the implant where some regions have more or stronger sources than others.Modern prostate implants achieve this using non-uniform distribution of (typically) identical sources.Afterloading and intra-cavitary systems: applicators,…

Source Design Requirements

All obvious…Sealed w/ durable encapsulation (esp. if reusable)Availability in quantity in appropriate strengthsExistence of a standard for source strengthExistence of standard dosimetry for archetype sourceVisibility in a variety of imaging modalitiesCompatability with existing source designsCompatability with existing source delivery devices

Source Design Features / Prostate

Also obvious…High dose per contained activity

(efficiency and possible reduced cost of isotope per source)

Relatively isotropic dose distribution for a source(since source orientation is possibly indeterminate)

Limited penetration to spare adjacent tissues(i.e. low energy)

Small unit size(since the prostate is not a large target)

Common Source Embodiments, IRadium in glass (Bell, 1903), in Pt-Ir (Domenici, 1907)

Sources with varied internal isotopic distribution:Uniform, dumbell (higher activity at ends), club (higher activity at one end)

137Cs: radium replacement (Isotope Produce Labs mmodel 67-6520) 3mm by 10-20mm long (TG43 form data: poster TU-D-T-617-05

and: Liu, et al. Med Phys 32:477- 428, 2004)182Ta wire: 0.2mm diameter with 0.1mm Pt sheath

(pre-TG43 dosimetry: Glasgow & Dillman, Med Phys 9:250-3, 1982)192Ir wire: 25/75 Ir/Pt, 0.1- 0.3mm diameter, 0.1mm sheath

(TG43/60 form data: Karaiskos, et al., Med. Phys. 28:156-166, 2001)192Ir seed, Best : 0.1mm core 30/70 Ir/Pt clad 0.2mm stainless steel, 3mm long192Ir seed, α-Ω : 0.3mm core 10/90 Ir/Pt clad 0.lmm Pt sheath , 3mm long

(TG43 form data, both seeds: Ballester, et al., Med Phys 32:3298-3304, 2004)

Common Source Embodiments, Ia198Au seed, Best, manufactured by EnglehardTG43U1 form data available, Sk standard?(Dauffy, et al., Med. Phys. 32:1579–88, 2005)

Common Source Embodiments, II125I and 103Pd seeds for prostate, brain, ocular, …Once: about twenty different 125I source designsAnd about seven different 103Pd source designsCommon dimensions: 0.8mm diameter by 4.5mm lengthCommon encapsulation: 0.05 - 0.08mm thick Ti tubesDifferences: Internal distribution and carrier of isotope, end-weld design, radio-opaque markers, & some noveltiesMotivations: Large market vs. enforceable patentsCompetition: Improved dosimetry & standards; source visibility, availability; reduced manufacturing costs

History of Standards: 125I & 103Pd

1970’s early and varied 125I dosimetry, MSKCC

1984: NIST: Ritz chamber exposure rate standard for 125I Aapp

1985: Kubo: Ti X-ray contamination in NIST’84 125I standard

1987: AAPM TG32 (Report 21) Sk air-kerma strength standard

1988: NIST Sk standard and adopted by Am. Endocurietherapy Soc. Theragenics Aapp assay for 103Pd, Yale & MSKCC dosimetry

1995: AAPM TG43: brachytherapy source dosimetry formalism

1998: AAPM ad hoc committee (Kubo) on 125I dosimetry reports onthe effects of NIST changing air-kerma strength standards

1998: AAPM ad hoc committee (Williamson): requisite dosimetry for new 125 I and 103 Pd brachytherapy sources

1999: Jan 01, NIST WAFAC Sk standard for 103Pd and 125I

1999: AAPM ad hoc committee (Williamson) on adopting the1999 NIST standard for (then) existing 125I sources

1999: AAPM ad hoc committee (Williamson) on transition fromuse of Aapp to Sk, re-emphasizing TG32

2000: AAPM draft Report 69 (Williamson) on NIST 103Pd Sk and Rx Am Brachytherapy Soc adopts 103Pd mono-Tx MPDRx of 125Gy

2000: October: NIST revises WAFAC Sk certificates from 1999

2001: 103Pd Rx new confusion; new TG43 in the works

2004: Revision AAPM TG43(U1), addressing several but not allavailable source designs for 103Pd and 125I, but correcting standard source dose-rate constants for WAFAC anomalies

2005: Revised recommendations for 103Pd and 125I prescription when using sources, source data, and formalism of TG43U1, updating Report 69(Williamson, et al., 2005 Med Phys 32(5):1424-1439.)

History of Standards: 125I & 103Pd

TG-43U1 Parameters:

Sk = air KERMA strength, U

Λ = dose-rate constant (cGy/hr-U)

G(r,θ) = geometry factor (cm-2)

gx(r) = radial dose function,X = Line or Point

F(r,θ) = anisotropy function

= anisotropy factor

-- in liquid water.

),()()

0,

0(

),(),( θθθθ rFrLg

rGrG

kSrD Λ=&

)()()(2

20 ranrPg

rr

kSrD φΛ=&

2D:

1D:

)(ranφ

kSrD /),( 00 θ&=Λ

L

P(r, θ )

y

θ θ2θ1

β

r0 = 1 cm

z

P(r 0,θ0)

θ0 = π/2

t

Nycomed / Amersham, OncoSeed TM , mdls 6711 & 6702, EchoSeedTM

Best Industries, BestR Iodine-125, model 2301NASI, ProsperaTM, MED3631-A/M

Imagyn isoStarTM, model 12501Mentor / Mills BioPharmaceuticals, model I125-SL/SHSource Tech Medical, 125ImplantTM, model STM12501

BeBig GmbH, SymmetraTM, model I25.S06IbT / IbT, InterSource125 TM (USA)

Implant Sciences, I-PlantTM, model 3500 & 3600Syncor, PharmaSeedTM, model BT-125-1(Pd), BT-125-2(Ag)

Draxis / DraxImage BrachySeedTM, model LS-1Isotron / Nucletron BV, selectSeed

IsoAid AdvantageTM 125IOthers?

Seeds & Manufacturers: 125I

Theragenics, TheraSeedTM 200NASI, model MED3633

Best Industries, BestR Palladium-103

IbT, InterSource103 TM

Mentor / Mills BioPharmaceuticals

BeBig

IsoAid AdvantageTM 103Pd (at AAPM 2005: SU-FF-T-12)

Others?

IsoRay, Inc., Model CS-1 131Cs source

Seeds & Manufacturers: 103Pd & 131Cs

Common features, dimensions

Thinner end welds in modern designs

Extended marker – location AND orientation

End loading for isotropic dose distribution

Silver vs other (e.g. organic resin) substrate and dosimetry

125I ,103Pd, & 131Cs Seeds, Themes

OncoSeed 6701/02 OncoSeed 6711 (also IsoAid)

EchoSeed 6733 TheraSeed 200

Mills I125-SL/SH 125I and 103Pd (unreleased) Idealized Mills source

Imagyn 12501 Nucletron selectSeed

Best Industries 2301 Syncor PharmaSeed BT-125-1,-2(Ag)

UroMed/BeBig Symmetra I25.S06 STM 125Implant STM12501

Implant Sciences 3500, silver marker Implant Sciences 3600, leaded glass marker

Implant 124Xe onto quartz tube surfaceNeutron activate to make:

125Xe (T1/2 17hr)125I

Wait several 125Xe half-livesCut to lengthAssemble

NASI MED3631/33 125I/103Pd Best Industries 2335

Draximage LS-1 IBT Intersource 125I/103Pd

RadioMed RadioCoil, 103Pd

IsoRay CS-1, 131Cs

Non-radioactive helical rhodium wireCyclotron activated via

103Rh(pn) 103PdCut to lengthsTG43 dosimetry for 0.5mm length

Along/away tables for other lengths (Meigooni, et al. 2004)

(at AAPM 2005: poster SU-FF-T-10)

Relative dosimetry similar to 6711-like sources (Avg energy 29-34kV)

Dose-rate constant nearing 125IInitial dose-rate like 103Pd (9.7 day T1/2)TG43 data and NIST calibration

(Murphy, et al. 2004)(at AAPM ‘05: SU-FF-T-15; TU-D-T-617-04)

Presently no enunciated Sk standard

Radial Dose Functions

0.0

0.2

0.4

0.6

0.8

1.0

1.2

0 2 4 6 8

r, cm

g(r)

MED3631-A/MMED3631-A/Smodel 6702

Radial Dose Functions

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

0 1 2 3 4 5 6 7

r, cmg(

r)

MED3633Mdl 200, TG43Mdl 200, Meigooni, et.al.Mdl 200, Chiu-Tsao & AndersonMdl 200, LuxtonMdl 200, Fontenla, et. al.Mdl 200, Sahoo & AndersonMdl 200, Russell

125I 103Pd

0

0.2

0.4

0.6

0.8

1

1.2

0 1 2 3 4 5 6 7 8

Distance, (cm)

Radi

al D

ose

Func

tion,

g(r

)

Amersham 6711

Imagyn isoSTAR

UroCor ProstaSeed

Syncor PharmaSeed

SourceTech 125Implant

Best Medical Model 2301

IBT InterSource125

0

0.2

0.4

0.6

0.8

1

1.2

0 1 2 3 4 5 6 7 8

Distance, (cm)

Radi

al D

ose

Func

tin, g

(r)

Amersham 6702

Mentor IoGold

UroMed Symmetra

Implant Sciences I-Plant

DraxImage BrachySeed

Amersham 6711

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

1.1

0 10 20 30 40 50 60 70 80 90

Polar angle, deg

F (r=

2, d

egre

es)

Amersham 6711Amersham 6702Mentor MED3631-A/MUroMed SymmetraImplant Sciences I-PlantDraxImage BrachySeed

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

1.1

0 10 20 30 40 50 60 70 80 90

Polar angle, deg

F (r=

2, d

egre

es)

Amersham 6711Imagyn IsoStarUroCor ProstaSeedSyncor PharmaSeedSourceTech 125ImpantBest Industries Model 2301IBT InterSource125

Activity adsorbed on a surface Activity absorbed in a volume

MED3631A/M (Wallace & Fan)

OncoSeed-6711 (TG43)

80cGy/hr

17

5

98

21

7

10422

8

9219

6

36

93

9720

7

MED3633 (Wallace & Fan)

TheraSeed-200 (TG43)

6321

92

6710

3

3912

51

3912

5

1

6321

92

6710

3

6711- equivalentsManufacturer Designation mCi ratio

Amersham 6711 0.320 1.000BeBig, GmBH I25.S06 0.297 0.928

Syncor BT-125-I 0.315 0.984Source Tech STM125-0 0.316 0.988

Implant Sciences Mdl 3500 0.303 0.947IBt, Belgium 125IL 0.301 0.941

Best Medical Mdl 2301 0.282 0.881NASI MED3631-A/M 0.286 0.894

III(Imagyn) 12501 0.349 1.091Mills/UroCor I125-SL 0.327 1.022

Draxis/Draximage LS-1 0.296 0.925Amersham 6702 0.296 0.925

Replicating a 6711 prostate implant using a different 125I source:Heintz, et al. (MP Apr ‘01) used ABS dosimetric (D100, D90, D80) and

volumetric (V200, V150, V100, V90, V80) quantifiers and proposed the conceptof a “6711-equivalent” activity for a given source that closely

reproduces the dose distribution when planned assuming 6711 sources.Of course, plans for a given source use the data for that source.

6711-equivalent Dose-rate x r2 (cGy-cm2/hr)

0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5 6 7

distance, cm

Dos

e-ra

te x

r2 , c

Gy-

cm2 /h

r

OncoSeed 6711

Symmetra I25.S06

PharmaSeed BT-125-I

125Implant STM125-0

I-Plant 3500

InterSource125, 125IL

Best125I, Model 2301

IoGold, MED3631-A/M

IsoStar, 12501

ProstaSeed, I125-LS

BrachySeed, LS1

OncoSeed, 6702

6711-equivalent Dose-rate x r2 (cGy-cm2/hr)

0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5 6 7

distance, cm

Dos

e-ra

te x

r2 , c

Gy-

cm2 /h

r

OncoSeed 6711

125Implant STM125-0

I-Plant 3500

Best125I, Model 2301

IoGold, MED3631-A/M

OncoSeed, 6702

Considerable effort in past decade has sought to improve design & manufacture of brachytherapy sources, particularly for 125I & 103Pd seeds.

Legacy designs / embodiments of 198Au, 192Ir, and 137Cs remain available.

New 131Cs source reported & in trials, awaits formal NIST Sk standard

The principles and desirable features of source design that were laid out in the early 20th century (Paterson & Parker, 1934) endure in current designs and in current development.

There have been advances in packaging: seed cartridges, pre-loaded needles and catheters, uniform and customized non-uniform spaced source strands, and automated needle loading systems.

Summary / Thanks