Skip to main content
Top
Published in: EJNMMI Research 1/2016

Open Access 01-12-2016 | Original research

Dependence of treatment planning accuracy in peptide receptor radionuclide therapy on the sampling schedule

Authors: Christian Maaß, Jan Philipp Sachs, Deni Hardiansyah, Felix M. Mottaghy, Peter Kletting, Gerhard Glatting

Published in: EJNMMI Research | Issue 1/2016

Login to get access

Abstract

Background

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 investigate the effect of reduced number of measurement points (i.e., gamma camera image acquisition or serum measurements) on treatment planning accuracy in PRRT using 111In-labeled-diethylenetriaminopentaacetic acid-octreotide (DTPAOC; Octreoscan™).

Methods

Pre-therapeutic biokinetic data of 15 NET patients were investigated using a recently developed physiologically based pharmacokinetic (PBPK) model. Two parameter sets were determined (standard or iterative approach) and used for calculation of time-integrated activity coefficients (TIACs) for the tumor, kidneys, liver, spleen, serum, and whole body. TIACs obtained using the full data sets were used as reference. To evaluate the effect of sampling on individual treatment planning, reduced sampling schedules were generated omitting either 1, 2, 3, or 4 organ and serum measurements or all serum measurements for each patient. Relative deviations (RDs) between these and reference TIACs were calculated and used as criterion for treatment planning accuracy. An RD < 0.1 was considered acceptable.

Results

When omitting serum measurements, TIAC accuracy remained acceptable (RD < 0.1) for the standard approach. The kidney TIACs could be estimated for both approaches with acceptable RDs using two time points (t = 4 h; 2 d); tumor RDs were <0.3. The iterative approach reduced the range of RD, but did not further reduce the number of needed measurement points (i.e., to achieve an RD <0.1). For both approaches RDs for liver, spleen and whole body were larger than 0.1. However, in the clinical setting these RDs are less relevant as liver and spleen are not organs at risk due to the low absorbed doses.

Conclusions

When using a priori information of a PBPK model structure combined with Bayesian information about PBPK model parameter distribution, the administered activity could be determined with acceptable accuracy using only two time points (4 h, 2 d) and thus allow a considerable reduction of needed data for individual dosimetry.
Literature
2.
go back to reference Chalkia MT, Stefanoyiannis AP, Prentakis A, Chatziioannou SN, Liotsou T, Geronikola-Trapali X, et al. Design and clinical implementation of a 99mTc-HYNICTOC-based dosimetric protocol in PRRT of NETs with 90Y-DOTATOC. Phys Med. 2014;30:e81. doi:10.1016/j.ejmp.2014.07.234.CrossRef Chalkia MT, Stefanoyiannis AP, Prentakis A, Chatziioannou SN, Liotsou T, Geronikola-Trapali X, et al. Design and clinical implementation of a 99mTc-HYNICTOC-based dosimetric protocol in PRRT of NETs with 90Y-DOTATOC. Phys Med. 2014;30:e81. doi:10.​1016/​j.​ejmp.​2014.​07.​234.CrossRef
3.
go back to reference Hardiansyah D, Maass C, Attarwala AA, Müller B, Kletting P, Mottaghy FM, et al. The role of patient-based treatment planning in peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2015. doi:10.1007/s00259-015-3248-6.PubMed Hardiansyah D, Maass C, Attarwala AA, Müller B, Kletting P, Mottaghy FM, et al. The role of patient-based treatment planning in peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2015. doi:10.​1007/​s00259-015-3248-6.PubMed
5.
go back to reference Strigari L, Konijnenberg M, Chiesa C, Bardies M, Du Y, Gleisner KS, et al. The evidence base for the use of internal dosimetry in the clinical practice of molecular radiotherapy. Eur J Nucl Med Mol Imaging. 2014;41(10):1976–88. doi:10.1007/s00259-014-2824-5.CrossRefPubMed Strigari L, Konijnenberg M, Chiesa C, Bardies M, Du Y, Gleisner KS, et al. The evidence base for the use of internal dosimetry in the clinical practice of molecular radiotherapy. Eur J Nucl Med Mol Imaging. 2014;41(10):1976–88. doi:10.​1007/​s00259-014-2824-5.CrossRefPubMed
6.
7.
go back to reference Minguez P, Flux G, Genolla J, Guayambuco S, Delgado A, Fombellida JC et al. Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with 131I-metaiodobenzylguanidine with implications for the activity to administer. Med Phys. 2015;42(7):3969-78. doi:10.1118/1.4921807. Minguez P, Flux G, Genolla J, Guayambuco S, Delgado A, Fombellida JC et al. Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with 131I-metaiodobenzylguanidine with implications for the activity to administer. Med Phys. 2015;42(7):3969-78. doi:10.​1118/​1.​4921807.
9.
go back to reference Kletting P, Müller B, Erentok B, Schmaljohann J, Behrendt FF, Reske SN, et al. Differences in predicted and actually absorbed doses in peptide receptor radionuclide therapy. Med Phys. 2012;39(9):5708–17. doi:10.1118/1.4747266.CrossRefPubMed Kletting P, Müller B, Erentok B, Schmaljohann J, Behrendt FF, Reske SN, et al. Differences in predicted and actually absorbed doses in peptide receptor radionuclide therapy. Med Phys. 2012;39(9):5708–17. doi:10.​1118/​1.​4747266.CrossRefPubMed
10.
go back to reference D’Argenio DZ. Optimal sampling times for pharmacokinetic experiments. J Pharmacokinet Biopharm. 1981;9(6):739–56.CrossRefPubMed D’Argenio DZ. Optimal sampling times for pharmacokinetic experiments. J Pharmacokinet Biopharm. 1981;9(6):739–56.CrossRefPubMed
13.
go back to reference Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med. 1999;40(2):37S–61S. Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med. 1999;40(2):37S–61S.
15.
go back to reference Lainez JM, Orcun S, Pekny JF, Reklaitis GV, Suvannasankha A, Fausel C, et al. Comparison of an assumption-free Bayesian approach with optimal sampling schedule to a maximum a posteriori approach for personalizing cyclophosphamide dosing. Pharmacotherapy. 2014;34(4):330–5. doi:10.1002/phar.1346.CrossRefPubMed Lainez JM, Orcun S, Pekny JF, Reklaitis GV, Suvannasankha A, Fausel C, et al. Comparison of an assumption-free Bayesian approach with optimal sampling schedule to a maximum a posteriori approach for personalizing cyclophosphamide dosing. Pharmacotherapy. 2014;34(4):330–5. doi:10.​1002/​phar.​1346.CrossRefPubMed
17.
go back to reference Youdarene R, Woillard JB, Prémaud A, Rousseau A, Debord J, Neely M, et al. Population pharmacokinetics and Bayesian estimation of mycophenolic acid exposure in heart transplant recipients: comparison of two approaches. J Heart Lung Transplant. 2013;32(4):S111. doi:10.1016/j.healun.2013.01.230.CrossRef Youdarene R, Woillard JB, Prémaud A, Rousseau A, Debord J, Neely M, et al. Population pharmacokinetics and Bayesian estimation of mycophenolic acid exposure in heart transplant recipients: comparison of two approaches. J Heart Lung Transplant. 2013;32(4):S111. doi:10.​1016/​j.​healun.​2013.​01.​230.CrossRef
18.
go back to reference Ogungbenro K, Dokoumetzidis A, Aarons L. Application of optimal design methodologies in clinical pharmacology experiments. Pharm Stat. 2009;8(3):239–52.CrossRefPubMed Ogungbenro K, Dokoumetzidis A, Aarons L. Application of optimal design methodologies in clinical pharmacology experiments. Pharm Stat. 2009;8(3):239–52.CrossRefPubMed
19.
20.
go back to reference Rippe B, Haraldsson B. Transport of macromolecules across microvascular walls: the two-pore theory. Physiol Rev. 1994;74(1):163–219.PubMed Rippe B, Haraldsson B. Transport of macromolecules across microvascular walls: the two-pore theory. Physiol Rev. 1994;74(1):163–219.PubMed
21.
go back to reference Barrett PH, Bell BM, Cobelli C, Golde H, Schumitzky A, Vicini P, et al. SAAM II: Simulation, Analysis, and Modeling software for tracer and pharmacokinetic studies. Metabolism. 1998;47(4):484–92.CrossRefPubMed Barrett PH, Bell BM, Cobelli C, Golde H, Schumitzky A, Vicini P, et al. SAAM II: Simulation, Analysis, and Modeling software for tracer and pharmacokinetic studies. Metabolism. 1998;47(4):484–92.CrossRefPubMed
24.
go back to reference Cremonesi M, Ferrari M, Bodei L, Tosi G, Paganelli G. Dosimetry in peptide radionuclide receptor therapy: a review. J Nucl Med. 2006;47(9):1467–75.PubMed Cremonesi M, Ferrari M, Bodei L, Tosi G, Paganelli G. Dosimetry in peptide radionuclide receptor therapy: a review. J Nucl Med. 2006;47(9):1467–75.PubMed
Metadata
Title
Dependence of treatment planning accuracy in peptide receptor radionuclide therapy on the sampling schedule
Authors
Christian Maaß
Jan Philipp Sachs
Deni Hardiansyah
Felix M. Mottaghy
Peter Kletting
Gerhard Glatting
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2016
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-016-0185-8

Other articles of this Issue 1/2016

EJNMMI Research 1/2016 Go to the issue