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Optimized Peptide Amount and Activity for ⁹⁰Y-Labeled DOTATATE Therapy
Peter Kletting1, Thomas Kull2, Christian Maaß3
1Department of Nuclear Medicine, Ulm University, Ulm, Germany peter.kletting@uniklinik-ulm.de.
Summary
Optimizing peptide and activity in peptide receptor radionuclide therapy improves treatment safety and efficacy. This personalized approach maximizes tumor dose while minimizing kidney and red marrow exposure for better patient outcomes.
Area of Science:
- Nuclear Medicine
- Radiopharmaceutical Therapy
- Pharmacokinetics
Background:
- Kidney absorbed dose limits (90)Y-DOTATATE therapy activity.
- Optimizing peptide and activity can improve tumor-to-kidney dose ratio.
- Receptor saturation varies between normal tissue and tumors.
Purpose of the Study:
- Develop a modeling method for treatment planning.
- Determine optimal peptide amount and activity combination for individual patients.
- Enhance efficacy and safety of (90)Y-DOTATATE therapy.
Main Methods:
- Developed a whole-body physiologically based pharmacokinetic (PBPK) model.
- Fitted model parameters to patient measurements ((111)In-DOTATATE).
- Quantified optimal peptide and activity for maximal tumor biologically effective dose (BED) within kidney and red marrow constraints.
Main Results:
- PBPK model accurately described biokinetic data.
- Significant inter-patient variability in tumor perfusion and receptor density observed.
- Identified optimal amounts (76-87 nmol) and activities (4.2-5.1 GBq) for meningioma and NET patients.
Conclusions:
- Optimizing both peptide amount and activity is crucial for (90)Y-DOTATATE therapy.
- Proposed modeling method enhances treatment efficacy and safety.
- Method adaptable for other peptide-based therapies.
