Modelling the internalisation process of prostate cancer cells for PSMA-specific ligands.
Compartmental modelling
Internalisation rate
PSMA
Surface plasmon resonance
Journal
Nuclear medicine and biology
ISSN: 1872-9614
Titre abrégé: Nucl Med Biol
Pays: United States
ID NLM: 9304420
Informations de publication
Date de publication:
Historique:
received:
05
02
2019
revised:
15
05
2019
accepted:
22
05
2019
pubmed:
2
7
2019
medline:
14
5
2020
entrez:
2
7
2019
Statut:
ppublish
Résumé
In prostate-specific membrane antigen (PSMA)-targeting radioligand therapy, small molecules are regularly internalised by the tumour cells. To determine the effectiveness of these ligands, the internalised fraction over time is derived from cell studies. Parameters, such as the ligand concentration and the number of cells, are experiment-specific and therefore a comparison between ligands is difficult. A more objective approach that allows better comparison is desirable. Therefore, the aim of this work was to develop a compartmental model that fully describes all relevant pharmacokinetic interactions of PSMA-specific ligands with prostate cancer cells. Internalisation studies were performed using the lymph node carcinoma of the prostate cell line LNCaP C4-2 and the prostatic carcinoma cell line PC-3. A new protocol was established for the determination of the PSMA-binding specificity by surface plasmon resonance (SPR). The experimental data in combination with parameters from literature were used for the modelling approach. A compartmental model which includes the relevant physiological mechanisms was developed. The basic model structure and some parameters originate from the literature. The PSMA-specific association and dissociation rates of Ga-PSMA-11 were measured using surface plasmon resonance technology. The ligand-induced internalisation and PSMA synthesis rates were estimated by fitting the developed model to experimental data obtained using LNCaP C4-2 cells. For all [ The presented approach is a prerequisite for better estimation and thus comparison of important ligand-cell interaction parameters, by combining SPR measurements, cell experiments and mathematical modelling. A compartmental model was developed for evaluation and comparison of PSMA-binding small molecules. A SPR protocol was established for the determination of PSMA-binding specificity.
Identifiants
pubmed: 31260881
pii: S0969-8051(19)30021-6
doi: 10.1016/j.nucmedbio.2019.05.003
pii:
doi:
Substances chimiques
Antigens, Surface
0
Gallium Isotopes
0
Gallium Radioisotopes
0
Ligands
0
Oligopeptides
0
gallium 68 PSMA-11
0
Edetic Acid
9G34HU7RV0
FOLH1 protein, human
EC 3.4.17.21
Glutamate Carboxypeptidase II
EC 3.4.17.21
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20-25Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.