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Differences in predicted and actually absorbed doses in peptide receptor radionuclide therapy
56
Citations
32
References
2012
Year
PharmacotherapyAkaike Information CriterionTreatment VerificationPharmacodynamic ModelingPre-clinical PharmacologyEndocrine OncologyRadiation MedicinePeptide TherapyRadiopharmaceutical TherapyClinical Radiation OncologyRadiation OncologyNuclear MedicineCancer ResearchRadiologyHealth SciencesTherapeutic Drug MonitoringPharmacokinetic ModelingRadiation TherapyMedicineRadionuclide TherapyAbsorbed DosesNon-peptide LigandPharmacologyDosimetryPeptide TherapeuticOncologyDifferent PeptidesDrug DiscoveryQuantitative Pharmacology
Purpose: An important assumption in dosimetry prior to radionuclide therapy is the equivalence of pretherapeutic and therapeutic biodistribution. In this study the authors investigate if this assumption is justified in sst2‐receptor targeting peptide therapy, as unequal amounts of peptide and different peptides for pretherapeutic measurements and therapy are commonly used. Methods: Physiologically based pharmacokinetic models were developed. Gamma camera and serum measurements of ten patients with metastasizing neuroendocrine tumors were conducted using 111 In‐DTPAOC. The most suitable model was selected using the corrected Akaike information criterion. Based on that model and the estimated individual parameters, predicted and measured 90 Y‐DOTATATE excretions during therapy were compared. The residence times for the pretherapeutic (measured) and therapeutic scenarios (simulated) were calculated. Results: Predicted and measured therapeutic excretion differed in three patients by 10%, 31%, and 7%. The measured pretherapeutic and therapeutic excretion differed by 53%, 56%, and 52%. The simulated therapeutic residence times of kidney and tumor were 3.1 ± 0.6 and 2.5 ± 1.2 fold higher than the measured pretherapeutic ones. Conclusions: To avoid the introduction of unnecessary inaccuracy in dosimetry, using the same substance along with the same amount for pretherapeutic measurements and therapy is recommended.
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