Trial reportPloS one2015
Physiologically Based Pharmacokinetic Modeling Is Essential in 90Y-Labeled Anti-CD66 Radioimmunotherapy.
Trial report in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- Uncertainty analysis of single-time-point organ dosimetry compared with the multi-time-point method in radioimmunotherapy.EJNMMI physics · 2026Article
- Multi-scale computational modeling towards efficacy in radiopharmaceutical therapies while minimizing side effects: Modeling of amino acid infusion.PLoS computational biology · 2025Article
- Digital twin-enhanced three-organ microphysiological system for studying drug pharmacokinetics in pregnant women.Frontiers in pharmacology · 2025Article
- Uncertainty Analysis of Time-Integrated Activity Coefficient in Single-Time-Point Dosimetry Using Bayesian Fitting Method.Nuclear medicine and molecular imaging · 2024Article
- Radiopharmaceutical transport in solid tumors via a 3-dimensional image-based spatiotemporal model.NPJ systems biology and applications · 2024Article
- Optimization of Radiolabeling of a [Cancers · 2023Article
- Current use and future potential of (physiologically based) pharmacokinetic modelling of radiopharmaceuticals: a review.Theranostics · 2022Review
- A modeling platform for the lymphatic system.Journal of theoretical biology · 2020Article
- SPECT-CT Imaging of Dog Spontaneous Diffuse Large B-Cell Lymphoma Targeting CD22 for the Implementation of a Relevant Preclinical Model for Human.Frontiers in oncology · 2020Article
- Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images.Molecular imaging and biology · 2018Article
- Dependence of treatment planning accuracy in peptide receptor radionuclide therapy on the sampling schedule.EJNMMI research · 2016Article
- Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionRadioimmunotherapy (RIT) with 90Y-labeled anti-CD66 antibody is used to selectively irradiate the red marrow (RM) before blood stem cell transplantation of acute leukemia patients. To calculate the activity to administer, time-integrated activity coefficients are required. These are estimated prior to therapy using gamma camera and serum measurements after injection of 111In labeled anti-CD66 antibody. Equal pre-therapeutic and therapeutic biodistributions are usually assumed to calculate the coefficients. However, additional measurements during therapy had shown that this assumption had to be abandoned. A physiologically based pharmacokinetic (PBPK) model was developed to allow the prediction of therapeutic time-integrated activity coefficients in eight patients.
aimsThe aims of the study were to demonstrate using a larger patient group 1) the need to perform patient-specific dosimetry in 90Y-labeled anti-CD66 RIT, 2) that pre-therapeutic and therapeutic biodistributions differ, and most importantly 3) that this difference in biodistributions can be accurately predicted using a refined model. MATERIALS AND
methodsTwo new PBPK models were developed considering fully, half and non-immunoreactive antibodies and constraints for estimating the RM antigen number. Both models were fitted to gamma camera and serum measurements of 27 patients. Akaike weights were used for model averaging. Time-integrated activity coefficients for total body, liver, spleen, RM and serum were calculated. Model-based predictions of the serum biokinetics during therapy were compared to actual measurements.
resultsVariability of the RM time-integrated activity coefficients ((37.3 ± 7.5) h) indicates the need for patient-specific dosimetry. The relative differences between pre-therapeutic and therapeutic serum time-activity curves were (-25 ± 16)%. The prediction accuracy of these differences using the refined PBPK models was (-3 ± 20)%.
conclusionIndividual treatment is needed due to biological differences between patients in RIT with 90Y-labeled anti-CD66 antibody. Differences in pre-therapeutic and therapeutic biokinetics are predominantly caused by different degrees of saturation due to different amounts of administered antibody. These differences could be predicted using the PBPK models.
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