M01413
Investigation of Simulation Accuracy of
Simbiology/Matlab for Area Under the Curve
Calculation in Peptide Receptor
Radionuclide Therapy
Deni Hardiansyah1, Rizal Maulana2, Adita Sutresno2,
Jaja M.Jabar2, Freddy Haryanto2, Gerhard Glatting1
1Medical
2Nuclear
Radiation Physics/Radiation Protection, Medical Faculty Mannheim, Heidelberg University, Germany
Physics and Biophysics Research Group, Physics Department, Institut Teknologi Bandung, Indonesia
Overview
•
Motivation
•
Aim
•
Materials and Methods
•
Results
•
Discussion
•
Conclusion
M.Sc. Deni Hardiansyah Slide 2 I 20/10/2014
Motivation
M.Sc. Deni Hardiansyah Slide 3 I 20/10/2014
Aim
M.Sc. Deni Hardiansyah Slide 4 I 20/10/2014
Materials and Methods (1)
PRRT
M.Sc. Deni Hardiansyah Slide 5 I 20/10/2014
Materials and Methods (2)
M.Sc. Deni Hardiansyah Slide 6 I 20/10/2014
Materials and Methods (3)
M.Sc. Deni Hardiansyah Slide 7 I 20/10/2014
Materials and Methods (3)
AUC Deviation
•
•
•
AUC Deviation is calculated to determine the difference of AUC
between SAAM and Simbiology/Matlab.
� � �� − �� ����2
��
��
��� � =
�� ����2
the following parameters were varied and the AUCs simulated: the
percentage of labeled to unlabeled peptide (1 %, 5 % and 10 %) and
administration type (bolus and 30 min of infusion).
Reliability test: AUCs calculated for 100 min with simulation time of
8000 min and of 100 min
M.Sc. Deni Hardiansyah Slide 8 I 20/10/2014
Result (1)
Graph From Simulation of Patient 4 (bolus 1%) in Simbiology/Matlab
M.Sc. Deni Hardiansyah Slide 9 I 20/10/2014
Result (2)
AUC Deviation (%)
Organ
Patient 1
Patient 2
Patient 3
Patient 4
Mean
SD
Kidney
1.0
1.4
-2.7
1.1
0.2
1.9
Tumor
14.4
16.4
17.4
2.0
12.6
7.1
Spleen
2.2
4.5
3.4
3.8
3.5
0.9
Liver
-3.0
-1.7
-6.5
-0.6
-3.0
2.5
Remainder
of Body
1.2
1.3
-3.2
0.7
0.0
2.1
M.Sc. Deni Hardiansyah Slide 10 I 20/10/2014
Results (3)
•
•
•
•
The model implementation was validated with AUC Deviation lower
than 4 % for kidney, spleen, liver and remainder of body.
For tumor AUCs the deviation was not in all cases lower than 5 %!
The reliability test for Simbiology/MATLAB showed that the first 100
min of time course led to 1 % error of AUC in the tumor.
In contrast, SAAM2 showed 0 % error for the same reliability test.
M.Sc. Deni Hardiansyah Slide 11 I 20/10/2014
Discussion
•
•
•
•
In most clinical study of radiotherapy, 5 % error is commonly used as
error limit of an acceptable accuracy of dosimetry.
For our PBPK model, care must be taken when using
Simbiology/Matlab, as for tumor AUCs the error was not in all cases
lower than 5 %.
Some investigation has done for different computational setting:
Algorithms: “ode45”, “ode15”, and “sundial”
Step size: 20.000 to 40.000
Tolerances: 1e-4 to 1e-8
Further Investigation are needed
M.Sc. Deni Hardiansyah Slide 12 I 20/10/2014
Conclusion
M.Sc. Deni Hardiansyah Slide 13 I 20/10/2014
References:
•
•
•
•
•
1.
Kletting, P., et al., Differences in predicted and actually absorbed doses in peptide receptor
radionuclide therapy. Med Phys, 2012. 39(9): p. 5708-17.
2.
Barrett, P.H., et al., SAAM II: Simulation, Analysis, and Modeling Software for tracer and
pharmacokinetic studies. Metabolism, 1998. 47(4): p. 484-92.
3.
Boston, R.C., P.C. Greif, and M. Berman, Conversational SAAM--an interactive program for
kinetic analysis of biological systems. Comput Programs Biomed, 1981. 13(1-2): p. 111-9.
4.
Cobelli, C. and D.M. Foster, Compartmental models: theory and practice using the SAAM II
software system. Adv Exp Med Biol, 1998. 445: p. 79-101.
5.
Nikos Papanikolaou, J.J.B., Arthur L. Boyer, Constantin Kappas, Eric Klein, T. Rock Mackie,
Michael Sharpe, Jake Van Dyk, Report of Task Group No. 65 of the Radiation Therapy Committee of
the American Association of Physicists in Medicine. American Asociation of Physicists in Medicine by
Medical Physics Publishing, 2004. 65.
M.Sc. Deni Hardiansyah Slide 14 I 20/10/2014
Simbiology/Matlab for Area Under the Curve
Calculation in Peptide Receptor
Radionuclide Therapy
Deni Hardiansyah1, Rizal Maulana2, Adita Sutresno2,
Jaja M.Jabar2, Freddy Haryanto2, Gerhard Glatting1
1Medical
2Nuclear
Radiation Physics/Radiation Protection, Medical Faculty Mannheim, Heidelberg University, Germany
Physics and Biophysics Research Group, Physics Department, Institut Teknologi Bandung, Indonesia
Overview
•
Motivation
•
Aim
•
Materials and Methods
•
Results
•
Discussion
•
Conclusion
M.Sc. Deni Hardiansyah Slide 2 I 20/10/2014
Motivation
M.Sc. Deni Hardiansyah Slide 3 I 20/10/2014
Aim
M.Sc. Deni Hardiansyah Slide 4 I 20/10/2014
Materials and Methods (1)
PRRT
M.Sc. Deni Hardiansyah Slide 5 I 20/10/2014
Materials and Methods (2)
M.Sc. Deni Hardiansyah Slide 6 I 20/10/2014
Materials and Methods (3)
M.Sc. Deni Hardiansyah Slide 7 I 20/10/2014
Materials and Methods (3)
AUC Deviation
•
•
•
AUC Deviation is calculated to determine the difference of AUC
between SAAM and Simbiology/Matlab.
� � �� − �� ����2
��
��
��� � =
�� ����2
the following parameters were varied and the AUCs simulated: the
percentage of labeled to unlabeled peptide (1 %, 5 % and 10 %) and
administration type (bolus and 30 min of infusion).
Reliability test: AUCs calculated for 100 min with simulation time of
8000 min and of 100 min
M.Sc. Deni Hardiansyah Slide 8 I 20/10/2014
Result (1)
Graph From Simulation of Patient 4 (bolus 1%) in Simbiology/Matlab
M.Sc. Deni Hardiansyah Slide 9 I 20/10/2014
Result (2)
AUC Deviation (%)
Organ
Patient 1
Patient 2
Patient 3
Patient 4
Mean
SD
Kidney
1.0
1.4
-2.7
1.1
0.2
1.9
Tumor
14.4
16.4
17.4
2.0
12.6
7.1
Spleen
2.2
4.5
3.4
3.8
3.5
0.9
Liver
-3.0
-1.7
-6.5
-0.6
-3.0
2.5
Remainder
of Body
1.2
1.3
-3.2
0.7
0.0
2.1
M.Sc. Deni Hardiansyah Slide 10 I 20/10/2014
Results (3)
•
•
•
•
The model implementation was validated with AUC Deviation lower
than 4 % for kidney, spleen, liver and remainder of body.
For tumor AUCs the deviation was not in all cases lower than 5 %!
The reliability test for Simbiology/MATLAB showed that the first 100
min of time course led to 1 % error of AUC in the tumor.
In contrast, SAAM2 showed 0 % error for the same reliability test.
M.Sc. Deni Hardiansyah Slide 11 I 20/10/2014
Discussion
•
•
•
•
In most clinical study of radiotherapy, 5 % error is commonly used as
error limit of an acceptable accuracy of dosimetry.
For our PBPK model, care must be taken when using
Simbiology/Matlab, as for tumor AUCs the error was not in all cases
lower than 5 %.
Some investigation has done for different computational setting:
Algorithms: “ode45”, “ode15”, and “sundial”
Step size: 20.000 to 40.000
Tolerances: 1e-4 to 1e-8
Further Investigation are needed
M.Sc. Deni Hardiansyah Slide 12 I 20/10/2014
Conclusion
M.Sc. Deni Hardiansyah Slide 13 I 20/10/2014
References:
•
•
•
•
•
1.
Kletting, P., et al., Differences in predicted and actually absorbed doses in peptide receptor
radionuclide therapy. Med Phys, 2012. 39(9): p. 5708-17.
2.
Barrett, P.H., et al., SAAM II: Simulation, Analysis, and Modeling Software for tracer and
pharmacokinetic studies. Metabolism, 1998. 47(4): p. 484-92.
3.
Boston, R.C., P.C. Greif, and M. Berman, Conversational SAAM--an interactive program for
kinetic analysis of biological systems. Comput Programs Biomed, 1981. 13(1-2): p. 111-9.
4.
Cobelli, C. and D.M. Foster, Compartmental models: theory and practice using the SAAM II
software system. Adv Exp Med Biol, 1998. 445: p. 79-101.
5.
Nikos Papanikolaou, J.J.B., Arthur L. Boyer, Constantin Kappas, Eric Klein, T. Rock Mackie,
Michael Sharpe, Jake Van Dyk, Report of Task Group No. 65 of the Radiation Therapy Committee of
the American Association of Physicists in Medicine. American Asociation of Physicists in Medicine by
Medical Physics Publishing, 2004. 65.
M.Sc. Deni Hardiansyah Slide 14 I 20/10/2014