Download Dose assessment in Nuclear Medicine Therapy

Dose assessment in
Nuclear Medicine
Therapy
Elisa Grassi
Medical Physics Dept
Santa Maria Nuova Hospital
Reggio Emilia
4° Meeting Internazionale
Imaging Metabolico PET per una Moderna Radioterapia
Reggio Emilia, 16-17 Aprile 2010
Importance of patient dosimetry
z
What is it?
It is a technique to simulate the radionuclide
therapy of a patient and to assess the internal
doses to organs and lesions.
z
What the aim?
At present to establish the highest dose to OARs
with no damage.
In the future it will be more and more oriented to
define the ratio between tumour dose and OAR
dose.
State of the art following the original
schema of MIRD16 and MIRD 21
z
z
z
Planar conjugate view counting is the most
widespread
method
Average
dose to organs/lesions
Hybrid planar + quantitative SPECT (or better if
Uniform activity distribution
SPECT-CT)
Fully 3D SPECT-CT based dosimetry
State of the art following the
MIRD17 schema
z
Non uniform activity distribution dosimetry at the
voxel level or voxel dosimetry
Wesley E. et al. J Nucl. Med. 1999 / Jeffrey A. Siegel et al. J Nucl. Med. 1999
Radiopharmaceuticals of excellence
for PRRT of NET
z 90Y/177Lu-DOTATOC
z 90Y/177Lu-DOTATATE
Analogues of
somatostatin
z 90Y/177Lu-DOTA-lanreotide
Dik J Kwekkeboom et al. Semin Nucl Med 2010
The future PRRT of NET ?
Alpha emitter labelled peptides: 213Bi-DOTATOC
Nayak TK et al. Nucl Med Biol 2007
Physical properties of beta emitters in
radionuclide therapy of NET
131I
177Lu
Half-life
8.04 d
Radiation
β-,γ (100%)
6.71 d
β-,γ (17%)
90Y
64 h
β-
177Lu-DOTATOC is preferred
Lesions’
diameter<2cm
Æ
182 keV
133 keV
933 keV
Mean beta energy
Lesions’
diameter >2cm
0.4 mmÆ
range
in water
Maximum beta energy
807 keV
range in water
90Y-DOTATOC
0.25 is
mmpreferred4.3 mm
Gabriel M et al. Q J nucl Med Mol Imaging 2010
497 keV
2284 keV
3.6 mm
1.9 mm
11.8 mm
range in perspex
3.1 mm
1.6 mm
10.3 mm
range in aluminium
1.6 mm
0.8 mm
5.2 mm
range in lead
0.5 mm
0.3 mm
1.6 mm
How to simulate PRRT?
Directly with 90Y-DOTATOC in course of therapy
SPECT-CT
Bremsstrahlung from
beta particles of 90Y
Fabbri C. et al. Cancer Biother Radiopharm, 2009
With 111In-DOTATOC (185MBq)
γ emission at 173keV and 247keV
(T1/2phys=67.4 h)
Planar imaging
and/or
SPECT-CT
How to simulate PRRT?
Directly with 177Lu-DOTATOC in course of therapy
Planar imaging
and/or
SPECT-CT
β/γ isotope
Sandstrom M et al. Eur J Nucl Med Mol Imaging 2010 / Cremonesi M et al QJ Nucl Med Mol Imaging 2010
The role of PET-CT imaging
68Ga
86Y-DOTATOC
/
for dosimetry ?
68Ga
/ 86Y-DOTATOC
68Ga
for diagnostics?
Pharmacokinetics of
90Y-DOTATOC
Urinary excretion
110
100
fraction of administered activity (%)
90
80
70
Blood clearance
60
50
40
30
20
Dmedia RM(90Y)=0.148Gy/GBq
10
0
0
10
20
30
t.p.i. (h)
40
50
blood sample
FTI tw o-exp
Dmedia KIDNEYs(90Y) α
30 x Dmedia RM(90Y)
Results of 111In planar dosimetry
for therapy with 90Y-DOTATOC
z
OAR par excellence are kidneys
High doses are absorbed also by:
z Liver
z Spleen
10
9
Gy/GBq for kidneys
z
Kidneys protection
reduces uptake
(-25% to - 65%)
8
7
-24%
6
5
4
3
2
1
0
no protected
kidneys
1
protected
kidneys
Organs and tumour doses estimates for
90Y / 177Lu-DOTATOC
z
Inserire istogramma articolo cremonesi
quarterly
Estimates of tumour and OAR doses per unit activity in patient undergoing PRRT trial
Cremonesi M et al QJ Nucl Med Mol Imaging 2010
Results of SPECT-CT dosimetry for
therapy with 90Y / 177Lu-DOTATOC
z
Fully 3D dosimetry: gamma-camera
characterization for quantitative purpose
Specific counts-to-activity
calibration curves for all isotopes
120
100
Calculation of specific S-voxel for
your case by Monte Carlo simulation
for voxeldosimetry
cps/MBq
80
111In
60
40
Other…
20
0
0
10
20
30
40
cc
volumes
50
60
70
…a physicist for implementation!
A study of dosimetric accuracy
111In
dosimetry
Sgouros G. et al Semin Nucl Med 2008
Simluations of activity distribution in a phantom
C-Planar= conjugate view planar
a planar quantitation method wherein Monte Carlo modeling
90YQ-Planar=
dosimetry
corrects for scatter and attenuation
Q-SPECT=quantitative SPECT
Fabbri C. et al. Cancer Biother Radiopharm, 2009
Dose limits for kidneys
z
z
z
From external radiation therapy it is:
z TD5,5=23 Gy e TD5,50=27 Gy
In internal radiation therapy the best quantity is the
estimate of the Biological Effective Dose (BED) and
the Equivalent Uniform Dose (EUD)
BED can be evaluated by simple dosimetry technique
(mean value), even if a better estimate of both BED
and EUD is furnished by voxel dosimetry (BED and
EUD maps)
T1 / 2 rep
β
2
BED = ∑ Di + ×
× ∑ Di
α (T1 / 2rep + T1 / 2eff ) i
i
α/β=2.6Gy for healthy renal tissue
Renal mono-exp decay assumption
Repair from sub-letal damage (2.8h for kidneys) Oehme L et al Nuklearmedizin 200
Radiobiological aspects
z
BED map Æ DVH of dose values
Æ DVH of BED values
P(Ψ): the probability
distribution of BED
values
where Ψ covers all
possible values for BED
∞
EUD = − α1 ln( ∫ P (Ψ )e −αΨ dΨ
0
The mean absorbed dose required to yield a surviving fraction equal to that
arising from the probability distribution of dose values (absorbed dose or
BED) given by the normalized DVH.
Sgouros G et al Semin nucl Med 2008
Combining dosimetry for target
radionuclide and external beam
therapies for organs and tumours
BED images from RRT
BED images from EXRT
Combination between two
dose distribution data
Information regarding the
spatial variability of
radiosensitivity within a
tumour
BED map using full patient-specific
data.
Prideux A. et al J Nucl Med 2007
Conclusions
•The role of dosimetry is fundamental to optimize the individual
activity chosen for treatment
•The dosimetric studies should improve the effective dose
delivered to the tumour mass without increasing toxicity
•The empirical approach should be left
z
What’s the future?
¾ To reach a more accurate computation level
¾ To optimize the tumours quantification through a
more precise imaging
¾ To implement standard software for 3D dosimetry
calculation and radiobiological considerations
¾ To implement new Monte Carlo based techniques
Thanks for your attention!