90Y-PET versus 90Y-Bremsstrahlung SPECT

S Walrand

Cliniques universitaires saint-Luc, Brussels

198Au rays scan 90Y bremsstrahlung scan

Simon and Feitelberg 1967

90Y TOF PET/CT

Lhommel et al. 2009

First 90Y microspheres injected intra-arterially imaging

Ford KW Phys Rev 1955

Hypothetical level diagram of 89Zr

as deduced from the neighboring nucleus 89Y.

A first excited 0+ state is expected

because of the large mutual interaction of the (g9/2)2 configuration.

2 or e+ e-

2x10-4 e+ observed Johnson et al. Phys Rev 1955

Nickles et al. IEEE TNM 2004

90Y micro-Derenzo phantom imaged

with a micro-PET P4 scanner

Selwyn et al. ARI 2006

e+: 3.2x10-5

Milestones in 90Y positron emission studies

The decay of 90Y has a minor branch to the 0+ excited state[1], followed by an internal e+ e- creation which happens in 32 out of one million decays [2]. Consequently, 90Y PET scan was proposed in order to assess the biodistribution [3] of 90Y-labelled therapeutic agents. A 61-year-old woman was referred for …………………………….

1. Ford. Phys Rev 1955 2. Selwyn et al. Appl Radiat Isot 2007 3. Nickles et al. IEEE Nucl Sci Symp Record 2004

30min

The additional liver low dose CT performed for the 90Y PET/CT evaluation

could be seen as an unjustified additional irradiation of the patient.

90Y: 40000 ± 5000 mSv CT: 2 mSv

amazing epoch

Lhommel, ...., Walrand EJNMMI 2010

Feasibility of 90Y TOF-PET based dosimetry in liver metastasis therapy using SIR-spheres.

true

TOF-PET

Dosimetry by kernel dose convolution

Relative activity

0 1

liver

2 3 4

True

mGy/MBQ

6.5 20.7 34.9 52.1 65.8

TOF-PET

mGy/MBQ

11. 24.6 37.3 52.6 63.5

Err

(%)

72 18.6 6.8 1.0 -3.4

FDG TOF-PET (day 1) FDG TOF-PET (day 57) 90Y TOF-PET (day 15)

Mean SUV = 5.96 Max. SUV =12.0

Mean SUV = 2.86 Max. SUV = 6.41

Mean dose: 85.3 Gy Max. dose:153.0 Gy

Mean dose: 29.9 Gy Max. dose: 37.7 Gy

necrotic tumour

90Y: 45min acquisition for 2 bed positions, i.e. 27cm

responding

progressive

90Y TOF-PET based dosimetry in liver metastasis therapy using resin spheres.

Lhommel, ...., Walrand EJNMMI 2010

HEF x D (Gy)

0 50 100 150 200 250

su

rviv

al

frac

tio

n

0·01

0·02

0·05

0·1

0·2

0·5

1

2

5

10

20

R=0·96

me

tab

olic

ra

tio

at

wee

k 7

po

st

thera

py

0·01

0·1

1

10

R2 = 0.96

Tumour early response-dose relationship in 90Y liver SIRT

Hb level (g/dL)8 10 12 14 16

HE

F

0

1

2

R=0·94

Walrand et al. EJNMMIres 2012

van Elmbt, Vandenberghe, Walrand et al. PMB 2011

Comparison of different crystals in 90Y PET

GSO

BGO

LYSO

Gemini TF LYSO TOF

Gemini TF LYSO

non-TOF

Allegro GSO

Exact HR+ BGO

36min 24min 12min

high count rate phantom hot spheres (1.7GBq 90Y)

van Elmbt, Vandenberghe, Walrand et al. PMB 2011

Comparison of different crystals in 90Y PET

TOF + PSF

TOF

PSF

5 10 15 20 25 30 35 40

0

20

40

60

80

100

hot sphere diameter (mm)

reco

ve

ry (

%)

Willowson et al. [13]

TOF + RR van Elmbt et al. [11]

Sfactor Stabin et al. [14-1]

QUEST multicentric study summary (Willowson et al. EJNMMI 2015)

Philips Gemini TF

Siemens Biograph mCT

GE Discovery 710 90Y Sfactor

recovery < 90Y Sfactor → local energy deposition method

Comparison of different crystals in 90Y-DOTATOC PET

low count rate kidney MIRD P19 phantom

modeling a 1h PET acquisition

after a typical first 90Y-DOTATOC therapy cycle

Walrand et al. JNM 2011

spine: 2.5MBq-12ml plastic vial

in 5cm diameter cylinder

filled with K2HPO4 solution

modeling bone attenuation

Kidney 35MBq Spline 100MBq

7ml tumours: 11,25 MBq

CT Gemini TF LYSO

Exact HR+ BGO

missing activity (radioactivity of LYSO)

50% plexiglas 50% H2O

H2O

Relative deviation: -18% -3%

dosimetry after each cycle

to optimize the next one

PET <> brems-SPECT in 90Y-DOTATOC therapy

Fabbri et al. Canc Bioth 2015

90Y-based PET and SPECT imaging

in locoregional brain treatment for high-grade gliomas

Fabbri et al. EJNMMI 2012

PET can provide superior image quality compared with brems-SPECT

and may enable reliable detection of extra-articular 90Y activity

Barber et al. JMI&RO 2013

90Y PET <> brems-SPECT post synovectomy

bin

0 50 100 150

co

un

ts

0.1

1

10

100

1000

10000

measured profile

source profile

scc profile

e+ e- pair production in LSO (X>1MeV) ?

(van Elmbt-Walrand)

Open issues in liver 90Y PET

spurious extra-hepatic counts

90Y-PET

90Y-TOF PET

acquired on a PET Biograph (courtesy of Dr. Ahmadzadehfar)

90Y vial in air true coincidences radial profile

Gate-GEANT4 simulations did not show

any significant e+e- creation in LSO

(Strydhorst et al. Med Phys 2016)

increasing tail

Internal bremsstrahlung:

a forgotten but significant effect in 90Y SPECT and PET imaging.

(Walrand et al. EANM Vienna 2017)

Aston 1927

1.E-7

1.E-6

1.E-5

1.E-4

1.E-3

1.E-2

1.E-1

1.E+0

1.E+1

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4

h2o brems G4

fit h2o brems

int brems [33]

int brems [28]

fit int brems

photo

n p

er

MeV

per

decay

E (M)

Venkataramaiah et al.1980

Cengiz et al.2004

Int. Bremss. not modeled in Geant4

effect discovery knowledge in nuclear medicine

e+ emission 1955 2004

int. bremss. 1927 2017

nucleus E field

β-

1.E-5

1.E-4

1.E-3

1.E-2

1.E-1

1.E+0

0 500 1000 1500

18F spectra

G4 511-Lu176

gauss 511keV

spectra fit

1.E-5

1.E-4

1.E-3

1.E-2

1.E-1

1.E+0

0 500 1000 1500

2.80E-03

gauss 511keV

fit

1.E-5

1.E-4

1.E-3

1.E-2

1.E-1

1.E+0

0 200 400 600 800

111In spectra

gauss 171keV

gauss 245keV

spectra f it

1.E-5

1.E-4

1.E-3

1.E-2

1.E-1

1.E+0

0 200 400 600 800

LYSO-PET 18F spectra

keV keV

arb

itra

ry u

nits

acquisition

171keV gauss

245keV gauss

fit

acquisition

G4 pileup

511keV gauss

fit

A B GSO-PET 111In spectra

acquisition

511keV gauss

fit

LSO-PET 18F spectra C

keV

Crystal scintillation exhibits long energy resolution tail

Internal bremsstrahlung:

a forgotten but significant effect in 90Y SPECT and PET imaging.

(Walrand et al. EANM Vienna 2017)

1.E-5

1.E+0

0 250 500 750

0.000

0.020

0.040

0.060

0.080

0.100

-45 -30 -15 0 15 30 45

acq

G4 int+h2o+gauss

G4 h2o+tail

G4 int+h2o+gauss

theory

cp

s p

er

bin

bin

GSO-PET 32P true cc rate radial profile A B

e-

>>250keV

bin

≈250 keV

32P vial

A

B

[450,650] keV

BUT

Internal bremsstrahlung:

a forgotten but significant effect in 90Y SPECT and PET imaging.

(Walrand et al. EANM Vienna 2017)

On the origin and on the reduction of spurious extrahepatic counts

observed in 90Y non-TOF PET imaging post radioembolization

(Walrand et al. EANM Vienna 2017)

Brems Lu176 LOR-TOF Brems Lu176 3D-RAMLA Brems Lu176 3D-RAMLA

Brems Lu176 3D-RAMLA Brems Lu176 LORDS-3D-RAMLA Brems Lu176 LOR-TOF

A B C

D E F

Spurious extrahepatic counts originate from randoms

not perfectly corrected in non-TOF PET

Gate-GEANT4 simulations with int+ext bremss.

198Au rays scan 90Y bremsstrahlung scan

Simon and Feitelberg 1967

0.00

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

50 100 150 200 250 300

Energy (keV)

Co

un

ts / k

eV

/ M

Bq

.s

Total counts

Primary photons

Scattered photons

Camera backscatter

Collimator scatter & penetration

Lead x-rays

Pb

[50,150]keV

geometrical

[50,150]keV

bac

k-sc

atte

rin

g

>150keV reduced using a medium energy or high energy collimator

90Y SPECT: contamination components

PET

3 10-5 decay emits positron

3D sensitivity: 2.5 10-2

0.8 10-6

1.5% decay emits bremsstrahlung X ray in [50,150] keV

Collimator sensitivity 10-4

1.5 10-6

SPECT

But + 9 10-6 scattered X rays

90Y SPECT: state of the art MC reconstruction

without scatter correction

with MC scatter correction Dewaraja et al. Med Phys 2017 Rault et al. Med Phys 2010

Germanium detector

Total 90Y bremss. in h2o

Not commercial available and collimator-camera dependent

The liver concentration of 0.34 MBq/mL used in the phantom was limited by radiation safety requirements of the regulatory authority at our institution.

Some radioprotection officers are imposing ALARA

can be a threat to imaging development (dead time, background)

and at the end, also a threat patient care

Gate 6.2 : Geant4 9.5-p01 + Geant4 9.6-p02 for atom de-excitations and fluorescence emissions

crystal

Lead housing

Pyrex lightguide

Mu-metal shielding

PMTs dynodes

90Y source in perpex

BGO camera based on Exact HR+ BGO-PMTs blocks + flat pinhole collimator

GE400 AC Crystal: NaI or BGO

90Y bremsstrahlung Monte Carlo modeling

Walrand et al. Front Oncol 2014

Pb

pri

mar

y

cam

era

bac

k-sc

atte

rin

g

NaI

PMT

elect. boards

β-

MC simulation of camera contaminating x-rays in bremsstrahlung imaging

signal >

scatter

scatter >

signal

E (keV)

0 100 200 300 400 500

Sig

na

l to

sca

tte

r ra

tio

0.1

1

10

100

MC simulation of the signal to scatter ratio

Pyrex

Walrand et al. Front Oncol 2014

Pb

pri

mar

y

BGO

PMT

elect. boards

β-

signal >

scatter

scatter >

signal

E (keV)

0 100 200 300 400 500

Sig

na

l to

sca

tte

r ra

tio

0.1

1

10

100

E (keV)

0 100 200 300 400 500

Sig

na

l to

sca

tte

r ra

tio

0.1

1

10

100

MC simulation of camera contaminating x-rays in bremsstrahlung imaging

MC simulation of the signal to scatter ratio

Walrand et al. Front Oncol 2014

signal >

scatter

scatter >

signal

E (keV)

0 100 200 300 400 500

Sig

na

l to

sca

tte

r ra

tio

0.1

1

10

100

Continuous energy tomography (CET)

Pb

pri

mar

y

BGO

PMT

elect. boards

β-

MC simulation of camera contaminating x-rays in bremsstrahlung imaging

MC simulation of the signal to scatter ratio

Walrand et al. Front Oncol 2014

90Y bremss. NaI-pinhole SPECT SIRT phantom evaluation

pinhole SPECT of longitudinally extended organ requires helical acquisition

helical non-circular acquisition, bed & camera manually moved

positions measured by 3 tape rulers 2 hours for the motions

medium energy thyroid pinhole: focal length too long

and 1/2 of the crystal area used

Walrand EJNMMI research 2011

Bremsstrahlung helical pinhole SPECT is superior to 90Y-TOF-PET

true 90Y TOF-PET helical PH SPECT

not commercially available

physicist patient

d

e

f a

36 min 3.6 min 1 min b c

90Y liver-SIRT

dosimetry in 3min helical PH SPECT

in catheterization room → optimization

Walrand EJNMMI research 2011

Perspective: dose optimization in catheterization room

Perspective: dose optimization in catheterization room

1/3 of maximal MAA based activity 3 min SPECT liver dosimetry if wrong delivery: catheter repositioning

or allowed activity to reach maximal safe liver dose

0.0

0.5

1.0

1.5

2.0

2.5

0.0 0.5 1.0 1.5 2.0 2.5

500ps-TOF & rand. est.

500ps-TOF & rand. sub.

activity/4 and 4x20min

GSO

L[Y]SO non-TOF

BGO

bremss. MEGP 2H SPECT ( T↑ S↑↑ SR=12mm)

100ps-TOF bremss. helical MEPH 2H SPECT ( S↓ versus MEGP)

936mm

van Elmbt ... PMB 2011

CT

kidney PRRT MIRD p19 Walrand ... JNM 2010

90Y activity (GBq in a liver lobe)

SNR

(2

0 m

in a

cqu

isit

ion

tim

e)

1936 mm

Walrand ... EJNMMI res 2011

true

90Y+L[Y]SO

Conclusions in 90Y imaging

PET supersedes commercial bremss. SPECT in all therapies

PET is usable for dosimetry purpose (using local energy deposition method)

TOF PET is preferable in post radioembolization delivery check

State of the art MC reconstruction bremss. SPECT approaches PET performance

Standard pinhole bremss. SPECT supersedes TOF-PET

and could be used in catheterization room for optimization

BGO (or GSO) pinhole bremss. SPECT is the optimal modality