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 Radiation Physics/Radiation Protection, Medical Faculty Mannheim, Heidelberg University, Germany 2Nuclear Physics and Biophysics Research Group, Physics Department, Institut Teknologi Bandung, Indonesia

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Overview

• Motivation

• Aim

• Materials and Methods

• Results

• Discussion

• Conclusion

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Motivation

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Aim

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PRRT

Materials and Methods (1)

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Materials and Methods (2)

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Materials and Methods (3)

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Materials and Methods (3)

AUC Deviation

• AUC Deviation is calculated to determine the difference of AUC

between SAAM and Simbiology/Matlab.

• 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

𝐴𝑈𝐶 𝐷𝑒𝑣𝑖𝑎𝑡𝑖𝑜𝑛 =𝐴𝑈𝐶 𝑠𝑖𝑚𝑏𝑖𝑜𝑙𝑜𝑔𝑦 − 𝐴𝑈𝐶(𝑆𝐴𝐴𝑀2)

𝐴𝑈𝐶(𝑆𝐴𝐴𝑀2)

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Result (1)

Graph From Simulation of Patient 4 (bolus 1%) in Simbiology/Matlab

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Result (2)

Organ

AUC Deviation (%)

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

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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.

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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

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Conclusion

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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.