التفاصيل البيبلوغرافية
| العنوان: |
Quantification of biochemical PSA dynamics after radioligand therapy with [177Lu]Lu-PSMA-I&T using a population pharmacokinetic/pharmacodynamic model |
| المؤلفون: |
Hinke Siebinga, Berlinda J. de Wit-van der Veen, Daphne M. V. de Vries-Huizing, Wouter V. Vogel, Jeroen J. M. A. Hendrikx, Alwin D. R. Huitema |
| المصدر: |
EJNMMI Physics, Vol 11, Iss 1, Pp 1-24 (2024) |
| بيانات النشر: |
SpringerOpen, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Medical physics. Medical radiology. Nuclear medicine |
| مصطلحات موضوعية: |
177Lu-PSMA-I&T, Population pharmacokinetic model, PKPD, PSA response, NONMEM, Prostate cancer, Medical physics. Medical radiology. Nuclear medicine, R895-920 |
| الوصف: |
Abstract Background There is an unmet need for prediction of treatment outcome or patient selection for [177Lu]Lu-PSMA therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Quantification of the tumor exposure–response relationship is pivotal for further treatment optimization. Therefore, a population pharmacokinetic (PK) model was developed for [177Lu]Lu-PSMA-I&T using SPECT/CT data and, subsequently, related to prostate-specific antigen (PSA) dynamics after therapy in patients with mCRPC using a pharmacokinetic/pharmacodynamic (PKPD) modelling approach. Methods A population PK model was developed using quantitative SPECT/CT data (406 scans) of 76 patients who received multiple cycles [177Lu]Lu-PSMA-I&T (± 7.4 GBq with either two- or six-week interval). The PK model consisted of five compartments; central, salivary glands, kidneys, tumors and combined remaining tissues. Covariates (tumor volume, renal function and cycle number) were tested to explain inter-individual variability on uptake into organs and tumors. The final PK model was expanded with a PD compartment (sequential fitting approach) representing PSA dynamics during and after treatment. To explore the presence of a exposure–response relationship, individually estimated [177Lu]Lu-PSMA-I&T tumor concentrations were related to PSA changes over time. Results The population PK model adequately described observed data in all compartments (based on visual inspection of goodness-of-fit plots) with adequate precision of parameters estimates ( |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2197-7364 |
| Relation: |
https://doaj.org/toc/2197-7364 |
| DOI: |
10.1186/s40658-024-00642-2 |
| URL الوصول: |
https://doaj.org/article/8fff240eb4dd480799fca12f85a0fb21 |
| رقم الانضمام: |
edsdoj.8fff240eb4dd480799fca12f85a0fb21 |
| قاعدة البيانات: |
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