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Verfasst von:Kletting, Peter [VerfasserIn]   i
 Glatting, Gerhard [VerfasserIn]   i
Titel:Optimized peptide amount and activity for 90Y-labeled DOTATATE therapy
Verf.angabe:Peter Kletting, Thomas Kull, Christian Maaß, Noeen Malik, Markus Luster, Ambros J. Beer, and Gerhard Glatting
Jahr:2016
Jahr des Originals:2015
Umfang:6 S.
Fussnoten:Gesehen am 08.04.2019 ; Im Titel ist "90" hochgestellt ; Published online: December 17, 2015
Titel Quelle:Enthalten in: Journal of nuclear medicine
Ort Quelle:New York, NY : Soc., 1964
Jahr Quelle:2016
Band/Heft Quelle:57(2016), 4, Seite 503-508
ISSN Quelle:2159-662X
 1535-5667
Abstract:In peptide receptor radionuclide therapy with 90Y-labeled DOTATATE, the kidney absorbed dose limits the maximum amount of total activity that can be safely administered in many patients. A higher tumor-to-kidney absorbed dose ratio might be achieved by optimizing the amount of injected peptide and activity, as recent studies have shown different degrees of receptor saturation for normal tissue and tumor. The aim of this work was to develop and implement a modeling method for treatment planning to determine the optimal combination of peptide amount and pertaining therapeutic activity for each patient. Methods: A whole-body physiologically based pharmacokinetic (PBPK) model was developed. General physiologic parameters were taken from the literature. Individual model parameters were fitted to a series (n = 12) of planar γ-camera and serum measurements (111In-DOTATATE) of patients with meningioma or neuroendocrine tumors (NETs). Using the PBPK model and the individually estimated parameters, we determined the tumor, liver, spleen, and red marrow biologically effective doses (BEDs) for a maximal kidney BED (20 Gy2.5) for different peptide amounts and activities. The optimal combination of peptide amount and activity for maximal tumor BED, considering the additional constraint of a red marrow BED less than 1 Gy15, was individually quantified. Results: The PBPK model describes the biokinetic data well considering the criteria of visual inspection, the coefficients of determination, the relative standard errors (<50%), and the correlation of the parameters (<0.8). All fitted parameters were in a physiologically reasonable range but varied considerably between patients, especially tumor perfusion (meningioma, 0.1-1 mL·g-1·min-1, and NETs, 0.02-1 mL·g-1·min-1) and receptor density (meningioma, 5-34 nmol·L-1, and NETs, 7-35 nmol·L-1). Using the proposed method, we identified the optimal amount and pertaining activity to be 76 ± 46 nmol (118 ± 71 μg) and 4.2 ± 1.8 GBq for meningioma and 87 ± 50 nmol (135 ± 78 μg) and 5.1 ± 2.8 GBq for NET patients. Conclusion: The presented work suggests that to achieve higher efficacy and safety for 90Y-DOATATE therapy, both the administered amount of peptide and the activity should be optimized in treatment planning using the proposed method. This approach could also be adapted for therapy with other peptides.
DOI:doi:10.2967/jnumed.115.164699
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.2967/jnumed.115.164699
 Volltext: http://jnm.snmjournals.org/content/57/4/503
 DOI: https://doi.org/10.2967/jnumed.115.164699
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:90Y-DOTATATE
 biologically effective dose (BED)
 PBPK modeling
 peptide amount
 PRRT
K10plus-PPN:1662965397
Verknüpfungen:→ Zeitschrift

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