Prediction of time-integrated activity coefficients in PRRT using simulated dynamic PET and a pharmacokinetic model

Hardiansyah, Deni; Attarwala, Ali Asgar; Kletting, Peter; Mottaghy, Felix M.; Glatting, Gerhard

doi:10.1016/j.ejmp.2017.06.024

Cited by 18 publications

(16 citation statements)

References 25 publications

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“…For the other three compartments, a shape of the time‐activity curve was assumed. It was taken that the curve for a kidney has steep growth and larger amplitude than in the tumor, but faster elimination, that is shorter retention than in the tumor . In the biokinetic model, it was assumed that all urine was collected in the third compartment, that is, in the urine bladder.…”

Section: Methodsmentioning

confidence: 99%

A five‐compartment biokinetic model for ⁹⁰Y‐DOTATOC therapy

et al. 2018

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Purpose Neuroendocrine tumors (NETs) are now routinely treated by radiopeptide targeted therapy using somatostatin receptor‐binding peptides such as 90Y‐ and 177Lu‐DOTATOC. The objective of this work was to develop a biokinetics model of 90Y labelled DOTATOC, which is applied in the therapy of NETs to estimate doses in kidney and tumor. Methods A multi‐compartment model described by two sets of differential equations, one set for the actual 30‐min infusion and the other set for the post‐infusion period was developed and activities were measured by liquid scintillation counting in blood (compartment 1) and the urine (compartment 3). The inter‐compartment transfer coefficients, λij, were varied to yield the best fit of the calculated to the measured time‐activity data and the 90Y‐DOTATOC time‐activity data in the five‐compartments comprising the human body were thus determined. The resulting time‐activity curves were integrated over the interval from 0 to 72 h post administration to obtain the number of radioactive decays in each compartment and, in case of the kidneys and tumor, then multiplied by the self‐dose 90Y beta particle absorbed fraction, determined by Monte Carlo (MC) simulation, the kidney and tumor absorbed doses. Results Transfer coefficients λij, were determined for five‐compartments for all patients. Time‐ activity curves of 90Y‐DOTATOC in 14 patients were determined, and two typical ones are shown graphically. Absorbed doses in the tumor and kidneys, obtained by the developed method, were determined. The mean absorbed dose in a kidney per unit of administered activity is 1.43 mGy/MBq (range 0.73–2.42 mGy/MBq). The tumor dose was determined as 30.94 mGy/MBq (range 20.05–42.31 mGy/MBq). Conclusion Analytical solution of a biokinetic model for 90Y‐DOTATOC therapy enabled determination of the transfer coefficients and derivation of time‐activity curves and kidney and tumor absorbed doses for 14 treated patients. The model can be applied to other radionuclides where elimination is predominantly through urine, which is often the case in radiopharmaceuticals.

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Section: Methodsmentioning

confidence: 99%

A five‐compartment biokinetic model for ⁹⁰Y‐DOTATOC therapy

et al. 2018

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“…They proved that 68 Ga-DOTATATE PET measurements could be used to predict the therapeutic biodistribution of 90 Y-DOTATATE with acceptable accuracy if all available information is integrated in PBPK. 40 − 42 …”

Section: New Reports Of Radiolabeled Amino Acid Based Molecules Used mentioning

confidence: 99%

Radiolabeled Peptides and Antibodies in Medicine

et al. 2020

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Radiolabeled peptides are a relatively new, very specific radiotracer group, which is still expanding. This group is very diverse in terms of peptide size. It contains very small structures containing several amino acids and whole antibodies. Moreover, radiolabeled peptides are diverse in terms of the binding aim and therapeutic or diagnostic applications. The majority of this class of radiotracers is utilized in oncology, where the same structure can be used in therapy and diagnostic imaging by varying the radionuclide. In this study, we collected new reports of radiolabeled peptide applications in diagnosis and therapy in oncology and other fields of medicine. Radiolabeled peptides are also increasingly being used in rheumatology, cardiac imaging, or neurology. The studies collected in this review concern new therapeutic and diagnostic procedures in humans and new structures tested on animals. We also performed an analysis of clinical trials, which concerns application of radiolabeled peptides and antibodies that were reported in the clinicaltrials.gov database between 2008 and 2018.

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“…Simulationsstudien mit PBPK-Ganzkörpermodellen zeigen jedoch die Möglichkeit auf, allein aufgrund einer einzigen Messung der Biodistribution (für die untersuchte Patientenpopulation) eine verlässliche Vorhersage der Pharmakokinetik während der Therapie zu erreichen [43,44].…”

Section: Beispiel: Hypothesengenerierung Für Die Vereinfachung Der Dounclassified

Pharmakokinetische Modellierung in der Nuklearmedizin

Kletting

Glatting

2018

Nuklearmediziner

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ZusammenfassungFür die nuklearmedizinische Dosimetrie wird die Kenntnis der Anzahl der Zerfälle des verwendeten Radionuklids im jeweiligen Gewebe oder dem betrachteten Volumenelement (Voxel) benötigt. Hierfür muss die Pharmakokinetik, also der entsprechende Zeitaktivitätsverlauf, bekannt sein, weil die Zahl der Zerfälle durch die mathematische Integration des Aktivitätsverlaufs über der Zeit berechnet werden kann. Da die Aktivität nur für einige wenige Zeitpunkte gemessen werden kann, muss die vollständige Pharmakokinetik für alle Zeitpunkte anhand von mathematischen Modellen geschätzt werden. Nur auf der Basis geeigneter Modelle können Vorhersagen der Pharmakokinetik zur Optimierung der Therapie erhalten werden.Diese Modelle unterscheiden sich in ihrer Komplexität aufgrund des im Modell enthaltenen Vorwissens über die zugrundeliegende Physiologie und der zur Verfügung stehenden Anzahl von Messpunkten: So gibt es modellunabhängige Varianten, einfache Kompartimentmodelle oder physiologisch basierte Kompartimentmodelle. In den Letzteren werden die mathematischen Kompartimente mit entsprechenden physiologischen Kompartimenten identifiziert, weshalb die Parameter des Modells physiologischen Größen entsprechen. Damit erlauben diese physiologisch basierten pharmakokinetischen (PBPK) Modelle nicht nur eine Kurvenanpassung an die Messwerte sondern zusätzlich auch die Simulation verschiedener therapeutischer Optionen als Basis zukünftiger Optimierungen der Therapie. Die unterschiedliche Komplexität des verwendeten Vorwissens für die verschiedenen Modelle beeinflusst die Anzahl der benötigten Messdaten und damit sowohl die Kosten als auch die Qualität der Ergebnisse. In dieser Übersicht werden zuerst verschiedene Arten von Modellen eingeführt und beobachterunabhängige Verfahren zur Auswahl des besten Modells basierend auf den gegebenen Messdaten diskutiert. Danach wird die Modellselektion am Beispiel des Akaike Informations-Kriteriums und von Qualitätskriterien für die Datenanpassung durch Modelle demonstriert. Des Weiteren werden Beispiele für den Einsatz von physiologisch basierten pharmakokinetischen Ganzkörpermodellen in der nuklearmedizinischen Dosimetrie zur Optimierung der Radionuklid-Therapie vorgestellt.

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Prediction of time-integrated activity coefficients in PRRT using simulated dynamic PET and a pharmacokinetic model

Cited by 18 publications

References 25 publications

A five‐compartment biokinetic model for ⁹⁰Y‐DOTATOC therapy

A five‐compartment biokinetic model for ⁹⁰Y‐DOTATOC therapy

Radiolabeled Peptides and Antibodies in Medicine

Pharmakokinetische Modellierung in der Nuklearmedizin

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Prediction of time-integrated activity coefficients in PRRT using simulated dynamic PET and a pharmacokinetic model

Cited by 18 publications

References 25 publications

A five‐compartment biokinetic model for 90Y‐DOTATOC therapy

A five‐compartment biokinetic model for 90Y‐DOTATOC therapy

Radiolabeled Peptides and Antibodies in Medicine

Pharmakokinetische Modellierung in der Nuklearmedizin

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A five‐compartment biokinetic model for ⁹⁰Y‐DOTATOC therapy

A five‐compartment biokinetic model for ⁹⁰Y‐DOTATOC therapy