Deni Hardiansyah

University of Indonesia | UI · Department of Physics

Purpose: This project aims to develop and evaluate a method for accurately determining time-integrated activities (TIAs) in single-time-point (STP) dosimetry for molecular radiotherapy. It performs a model selection (MS) within the framework of the nonlinear mixed-effects (NLME) model (MS-NLME). Methods: Biokinetic data of [111In]In-DOTATATE act...

Purpose: Personalized treatment planning in Molecular Radiotherapy (MRT) with accurately determining the absorbed dose is highly desirable. The absorbed dose is calculated based on the Time-Integrated Activity (TIA) and the dose conversion factor. A crucial unresolved issue in MRT dosimetry is which fit function to use for the TIA calculation. A d...

Immunotherapy with checkpoint inhibitors with Pembrolizumab shows potential to be used as a first-line in cancer treatment. A biodistribution study could be used to maximize efficacy and minimize the risk of the treatment. Therefore, it is necessary to describe the biodistribution of the 89Zr-Pembrolizumab. This study aims to create a mathematical...

Note: Please see pdf for full abstract with equations. Purpose This project aims to develop and evaluate a method for accurately determining time-integrated activities (TIAs) in single-time-point (STP) dosimetry for molecular radiotherapy (MRT). It performs a Model Selection (MS) within the framework of the Non-Linear Mixed-Effects (NLME) model (MS...

Introduction Estimation of accurate time-integrated activity coefficients (TIACs) and radiation absorbed doses (ADs) is desirable for treatment planning in peptide-receptor radionuclide therapy (PRRT). This study aimed to investigate the accuracy of a simplified dosimetry using a physiologically-based pharmacokinetic (PBPK) model, a nonlinear mixed...

Purpose To develop a minimal physiologically-based pharmacokinetic (mPBPK) model in quantifying the relationships between the charge and pharmacokinetics (PK) of therapeutic monoclonal IgG antibody (TMAb). Methods PK data used in this study were native IgG and five humanized anti-HCVE2-IgG antibodies in rats. Different models that related the effe...

Abstract Background The calculation of time-integrated activities (TIAs) for tumours and organs is required for dosimetry in molecular radiotherapy. The accuracy of the calculated TIAs is highly dependent on the chosen fit function. Selection of an adequate function is therefore of high importance. However, model (i.e. function) selection works mor...

The purpose of this study was to identify the most important physiologically-based pharmacokinetic (PBPK) model parameters determining the absorbed dose (AD) in prostate-specific membrane antigen (PSMA) therapy. The extended-Sobol’ global sensitivity analysis method was used to analyze the sensitivity of the PBPK model parameters obtained from 3 pa...

Calculation of accurate time-integrated activity coefficients (TIACs) is desirable in nuclear medicine dosimetry. The accuracy of the calculated TIACs is highly dependent on the fit function. However, systematic studies of determining a good function for peptide-receptor radionuclide therapy (PRRT) in different patients have not been reported in th...

This study aimed to determine the organ at risk (OAR) of ¹⁷⁷Lu-HA in liver cancer therapy using the biodistribution study and model selections method. Administration of ¹⁷⁷Lu-HA was carried out directly on the intra-artery of Wistar rat liver by surgery. Pharmacokinetics data of ¹⁷⁷Lu-HA in Wistar rats from different organs, such as liver, kidneys,...

The aim of this study was to investigate the effect of different radiopharmaceutical drugs on the performance of translation method of time-integrated activity coefficient (TIAC) from mice to humans. ¹⁷⁷Lu-DOTA-Trastuzumab (Tras) percentage of injected dose (%ID) in Swiss Webster mice at 1, 2, 3, 4, 24, and 48 hours p.i was used to fit the paramete...

This study aimed to determine the effect of the physiological parameters (PP) to the optimal administration of Lysine/Arginine for kidney protection during peptide-receptor radionuclide therapy (PRRT) using the Physiologically-based Pharmacokinetic (PBPK) model. Modeling of PBPK was performed to describe the bio-distribution of Lysine/Arginine in t...

In this study, we implemented for the first time the Population and Covariate Model (POPCOV) to simplify the Individual Treatment Planning (ITP) process in PRRT with minimal Physiologically based Pharmacokinetic (mPBPK) model. POPCOV method was used to predict the unknown parameters of the PBPK model using the individual covariates. Stepwise select...

In this study, we identified the most important physiologic parameters determining the variability of the organ at risk and tumor absorbed doses (ADs) in Peptide-receptor radionuclide therapy (PRRT). Therefore, a global sensitivity analysis (GSA) with Sobol method and a physiologically-based pharmacokinetic (PBPK) model were used. A whole-body PBPK...

This study aims to identify the most important parameters in the Physiologically-Based Pharmacokinetic (PBPK) model of Peptide Receptor Radionuclide Therapy (PRRT). By knowing the size of the contribution of physiological parameters to the PBPK model, it can reduce the variability of the absorbed dose (AD) in organs at risk, such as the kidney and...

Purpose: The knowledge of the contribution of anatomical and physiological parameters to interindividual pharmacokinetic differences could potentially be used to improve individualized treatment planning for radionuclide therapy. The aim of this study was therefore to identify the physiologically based pharmacokinetic (PBPK) model parameters that d...

Objective: The performance characteristics of the SPECT sub-system S102 of the ALBIRA II PET/SPECT/CT are analyzed for the 80 mm field of view (FOV) to evaluate the potential in-vivo imaging in rats, based on measurements of the system response for the commonly used Technetium-99 m (99mTc) in small animal imaging. Methods: The ALBIRA II tri-modal µ...

Dose selection of monoclonal antibodies (mAb) in pediatric subjects is often based on the assumption that disease and pharmacodynamics in children are similar to those in adult, and only prior information of pharmacokinetic (PK) data in adults is used for dose selection. The PK of the mAbs is affected by the body size, and other patient‐specific fa...

Chimeric antigen receptor T‐cells (CART) is a new and promising cancer therapy. However, severe toxicity due to cytokine release syndrome (CRS) in CART‐treated patients highlighted the possible danger of this new therapy. Disease burden and CART doses are the potential factors associated with the CRS but the detail relationships between these facto...

In this study, we developed a first minimal physiologically-based pharmacokinetic (mPBPK) model to investigate the complex interaction effects of endocytosis rate/FcRn binding affinity at both acidic/physiological pH on the pharmacokinetics (PK) of the anti-VEGF IgG1 antibodies. The data used in this study were the PK of the native IgG and humanize...

The aim of this study was to investigate neonatal Fc receptor (FcRn) concentration developmental pharmacology in adult and pediatric subjects using minimal physiologically-based pharmacokinetic (mPBPK) modelling. Three types of pharmacokinetic (PK) data for three agents (endogenous/exogenous native IgG, bevacizumab and palivizumab) were used. The a...

Aim: A method to determine the point spread function (PSF) of an imaging system based on a set of 3- dimensional Gaussian functions is presented for a robust estimation of the recovery corrections for accurate activity quantification in PET/SPECT systems. Materials and Methods: The spatial resolution of the ALBIRA II PET subsystem was determined us...

Purpose: The aim of this study was to develop a two-pore minimum physiologically-based pharmacokinetic (mPBPK) model in describing the pharmacokinetic (PK) of therapeutic monoclonal antibody (TMAb) in human subjects. Methods: PK data used in this study were endogenous/exogenous native IgG and two TMAbs (palivizumab and Motavizumab-YTE) in normal...

Purpose: To investigate the accuracy of predicted time-integrated activity coefficients (TIACs) in peptide-receptor radionuclide therapy (PRRT) using simulated dynamic PET data and a physiologically based pharmacokinetic (PBPK) model. Methods: PBPK parameters were estimated using biokinetic data of 15 patients after injection of (152±15)MBq of (...

Aim: In this study the performance characteristics of the Albira II PET sub-system and the response of the system for the following radionuclides (18)F, (68)Ga and (64)Cu was analyzed. Materials and methods: The Albira II tri-modal system (Bruker BioSpin MRI GmbH, Ettlingen, Germany) is a pre-clinical device for PET, SPECT and CT. The PET sub-sy...

Aim: To investigate the accuracy of treatment planning in peptide-receptor radionuclide therapy (PRRT) based on simulated PET data (using a PET noise model) and a physiologically based pharmacokinetic (PBPK) model. Methods: The parameters of a PBPK model were fitted to the biokinetic data of 15 patients. True mathematical phantoms of patients (M...

Purpose: The aim of this study was to investigate the accuracy of PET-based treatment planning for predicting the time-integrated activity coefficients (TIACs). Methods: The parameters of a physiologically based pharmacokinetic (PBPK) model were fitted to the biokinetic data of 15 patients to derive assumed true parameters and were used to construc...

The aim of this work was to evaluate the sensitivity of time-integrated activity coefficients (TIACs) on the erroneously chosen prior knowledge in a physiologically based pharmacokinetic (PBPK) model used for treatment planning in peptide receptor radionuclide therapy (PRRT). Parameters of the PBPK model were fitted to the biokinetic data of 15 pat...

Published online: http://www.medphys.org/PhDAbstracts/hardiansyahphd.pdf Peptide-receptor radionuclide therapy (PRRT) for neuroendocrine tumors has shown to be an effective therapeutic option in addition to chemotherapy or external beam therapy. PRRT uses radiolabeled somatostatin analogues to target the somatostatin receptors (most commonly subty...

Background: Accurate treatment planning is recommended in peptide-receptor radionuclide therapy (PRRT) to minimize the toxicity to organs at risk while maximizing tumor cell sterilization. The aim of this study was to quantify the effect of different degrees of individualization on the prediction accuracy of individual therapeutic biodistributions...

Peptide receptor radionuclide therapy (PRRT) plays an important role in the treatment of neuroendocrine tumors (NET). Pre-therapeutic dosimetry using the area under the measured time-activity curve (AUC) is important. The sampling schedule for this dosimetry determines the accuracy and reliability of the obtained AUC. The aim of this study was to i...

Purpose: Peptide receptor radionuclide therapy (PRRT) is commonly performed in the treatment of neuroendocrine tumors (NET), where somatostatin analogs (DOTATATE) are radiolabeled with (90)Y, (68)Ga or (111)In for pre-therapeutic and therapeutic purposes. Quantitative evaluation of the biokinetic data can be performed by using physiologically base...

Aim: Accurate estimation of time-integrated activity coefficients is essential for treatment planning in radioimmunotherapy (RIT). Recently it was shown that for the estimation of these coefficients, the application of physiologically based pharmacokinetic (PBPK) models is advantageous over the standard approach (sums of exponential functions) [1,...

Aim: The aim of this study was (1) to determine population parameter values and using these parameter values (2) to quantify the effect of sampling schedules with differing sizes on the estimation of time-integrated activity coefficients in PRRT with 111In DTPAOC in 15 patients. Materials and Methods: Fifteen patients with proven neuroendocrine t...

Hidayati et al., RDNI,Vol. 2, No.1, 2015, pp.49-57

Prism is a non-commercial Radiotherapy Treatment Planning System (RTPS) develop by Ira J. Kalet from Washington University. Inhomogeneity factor is included in Prism TPS dose calculation. The aim of this study is to investigate the sensitivity of dose calculation on Prism using Monte Carlo simulation. Phase space source from head linear accelerator...

Ziel: Das Ziel dieser Arbeit ist die Verbesserung der Vorhersagegenauigkeit therapeutischer Biodistributionen mittels populationsbasierter pharmakokinetischer Modellierung bei der Radioimmuntherapie Methodik: Für 26 Patienten mit akuter myeloischer und lymphatischer Leukämie wurde die Biodistribution radiomarkierter (prätherapeutisch: In-111; th...