M01413

Investigation of Simulation Accuracy of

Simbiology/Matlab for Area Under the Curve

Calculation in Peptide Receptor

Radionuclide Therapy

Deni Hardiansyah1_{, Rizal Maulana}2_{, Adita Sutresno}2_,

Jaja M.Jabar2_{, Freddy Haryanto}2_{, Gerhard Glatting}1

Overview

• Motivation

• Aim

• Materials and Methods

• Results

• Discussion

M.Sc. Deni Hardiansyah Slide 3 I 20/10/2014

M.Sc. Deni Hardiansyah Slide 5 I 20/10/2014 PRRT

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.

• 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 9 I 20/10/2014

Result (1)

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

M.Sc. Deni Hardiansyah Slide 11 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.

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

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.