Quantification of biochemical PSA dynamics after radioligand therapy with [177Lu]Lu-PSMA-I&T using a population pharmacokinetic/pharmacodynamic model

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: EJNMMI Physics, Vol 11, Iss 1, Pp 1-24 (2024)
Druh dokumentu: article
ISSN: 2197-7364
DOI: 10.1186/s40658-024-00642-2
Popis: 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 (
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