| Autor: |
Jiménez-Franco LD; ABX-CRO Advanced Pharmaceutical Services Forschungsgesellschaft mbH, Dresden, Germany., Glatting G; Department of Nuclear Medicine, Ulm University, Ulm, Germany.; Medical Radiation Physics, Department of Nuclear Medicine, Ulm University, Ulm, Germany; and., Prasad V; Department of Nuclear Medicine, Ulm University, Ulm, Germany., Weber WA; Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany., Beer AJ; Department of Nuclear Medicine, Ulm University, Ulm, Germany., Kletting P; Department of Nuclear Medicine, Ulm University, Ulm, Germany peter.kletting@uniklinik-ulm.de.; Medical Radiation Physics, Department of Nuclear Medicine, Ulm University, Ulm, Germany; and. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2021 Jan; Vol. 62 (1), pp. 92-98. Date of Electronic Publication: 2020 Jul 09. |
| DOI: |
10.2967/jnumed.120.245068 |
| Abstrakt: |
The aim of this work was to determine a minimal tumor perfusion and receptor density for 177 Lu-DOTATATE therapy using physiologically based pharmacokinetic (PBPK) modeling considering, first, a desired tumor control probability (TCP) of 99% and, second, a maximal tolerated biologically effective dose (BED max ) for organs at risk (OARs) in the treatment of neuroendocrine tumors and meningioma. Methods: A recently developed PBPK model was used. Nine virtual patients (i.e., individualized PBPK models) were used to perform simulations of pharmacokinetics for different combinations of perfusion (0.001-0.1 mL/g/min) and receptor density (1-100 nmol/L). The TCP for each combination was determined for 3 different treatment strategies: a standard treatment (4 cycles of 7.4 GBq and 105 nmol), a treatment maximizing the number of cycles based on BED max for red marrow and kidneys, and a treatment having 4 cycles with optimized ligand amount and activity. The red marrow and the kidneys (BED max of 2 Gy 15 and 40 Gy 2.5 , respectively) were assumed to be OARs. Additionally, the influence of varying glomerular filtration rates, kidney somatostatin receptor densities, tumor volumes, and release rates was investigated. Results: To achieve a TCP of at least 99% in the standard treatment, a minimal tumor perfusion of 0.036 ± 0.023 mL/g/min and receptor density of 34 ± 20 nmol/L were determined for the 9 virtual patients. With optimization of the number of cycles, the minimum values for perfusion and receptor density were considerably lower, at 0.022 ± 0.012 mL/g/min and 21 ± 11 nmol/L, respectively. However, even better results (perfusion, 0.018 ± 0.009 mL/g/min; receptor density, 18 ± 10 nmol/L) were obtained for strategy 3. The release rate of 177 Lu (or labeled metabolites) from tumor cells had the strongest effect on the minimal perfusion and receptor density for standard and optimized treatments. Conclusion: PBPK modeling and simulations represent an elegant approach to individually determine the minimal tumor perfusion and minimal receptor density required to achieve an adequate TCP. This computational method can be used in the radiopharmaceutical development process for ligand and target selection for specific types of tumors. In addition, this method could be used to optimize clinical trials.
(© 2021 by the Society of Nuclear Medicine and Molecular Imaging.) |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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