Cargando…

Intra-individual dynamic comparison of (18)F-PSMA-11 and (68)Ga-PSMA-11 in LNCaP xenograft bearing mice

Recently, a (18)F-labeled derivative of the widely used (68)Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although (18)F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its d...

Descripción completa

Detalles Bibliográficos
Autores principales: Piron, Sarah, Verhoeven, Jeroen, Descamps, Benedicte, Kersemans, Ken, De Man, Kathia, Van Laeken, Nick, Pieters, Leen, Vral, Anne, Vanhove, Christian, De Vos, Filip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713063/
https://www.ncbi.nlm.nih.gov/pubmed/33273603
http://dx.doi.org/10.1038/s41598-020-78273-7
_version_ 1783618508946407424
author Piron, Sarah
Verhoeven, Jeroen
Descamps, Benedicte
Kersemans, Ken
De Man, Kathia
Van Laeken, Nick
Pieters, Leen
Vral, Anne
Vanhove, Christian
De Vos, Filip
author_facet Piron, Sarah
Verhoeven, Jeroen
Descamps, Benedicte
Kersemans, Ken
De Man, Kathia
Van Laeken, Nick
Pieters, Leen
Vral, Anne
Vanhove, Christian
De Vos, Filip
author_sort Piron, Sarah
collection PubMed
description Recently, a (18)F-labeled derivative of the widely used (68)Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although (18)F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with (18)F-PSMA-11 or (68)Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding. Mice bearing LNCaP or PC-3 xenografts each received ± 3.7 MBq (18)F-PSMA-11 and (68)Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as ± 15 MBq (18)F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUV(mean), SUV(max), TBR(mean) and TBR(max)). Mice underwent ex vivo biodistribution where (18)F-PSMA-11 activity was measures in excretory organs (kidneys, bladder and liver) as well as bone fragments (femur, humerus, sternum and skull) to evaluate bone uptake. The dissociation constant (K(d)) of (18)F-PSMA-11 and (68)Ga-PSMA-11 was 2.95 ± 0.87 nM and 0.49 ± 0.20 nM, respectively. Uptake parameters were significantly higher in LNCaP compared to PC-3 xenografts for both (18)F-PSMA-11 and (68)Ga-PSMA-11, while no difference was found for (18)F-FDG uptake (except for SUV(max)). Tumor uptake of (18)F-PSMA-11 showed a similar trend over time as (68)Ga-PSMA-11, although all uptake parameter curves of the latter were considerably lower. When comparing early (60 min p.i.) to delayed (150 min p.i.) imaging for both radiotracers individually, TBR(mean) and TBR(max) were significantly higher at the later timepoint, as well as the SUV(max) of (68)Ga-PSMA-11. The highest %ID/g was determined in the kidneys (94.0 ± 13.6%ID/g 1 h p.i.) and the bladder (6.48 ± 2.18%ID/g 1 h p.i.). No significant increase in bone uptake was seen between 1 and 2 h p.i. Both radiotracers showed high affinity for the PSMA receptor. Over time, all uptake parameters were higher for (18)F-PSMA-11 compared to (68)Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late (18)F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of (18)F-PSMA-11 as well as no significant increase in bone uptake.
format Online
Article
Text
id pubmed-7713063
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-77130632020-12-03 Intra-individual dynamic comparison of (18)F-PSMA-11 and (68)Ga-PSMA-11 in LNCaP xenograft bearing mice Piron, Sarah Verhoeven, Jeroen Descamps, Benedicte Kersemans, Ken De Man, Kathia Van Laeken, Nick Pieters, Leen Vral, Anne Vanhove, Christian De Vos, Filip Sci Rep Article Recently, a (18)F-labeled derivative of the widely used (68)Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although (18)F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with (18)F-PSMA-11 or (68)Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding. Mice bearing LNCaP or PC-3 xenografts each received ± 3.7 MBq (18)F-PSMA-11 and (68)Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as ± 15 MBq (18)F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUV(mean), SUV(max), TBR(mean) and TBR(max)). Mice underwent ex vivo biodistribution where (18)F-PSMA-11 activity was measures in excretory organs (kidneys, bladder and liver) as well as bone fragments (femur, humerus, sternum and skull) to evaluate bone uptake. The dissociation constant (K(d)) of (18)F-PSMA-11 and (68)Ga-PSMA-11 was 2.95 ± 0.87 nM and 0.49 ± 0.20 nM, respectively. Uptake parameters were significantly higher in LNCaP compared to PC-3 xenografts for both (18)F-PSMA-11 and (68)Ga-PSMA-11, while no difference was found for (18)F-FDG uptake (except for SUV(max)). Tumor uptake of (18)F-PSMA-11 showed a similar trend over time as (68)Ga-PSMA-11, although all uptake parameter curves of the latter were considerably lower. When comparing early (60 min p.i.) to delayed (150 min p.i.) imaging for both radiotracers individually, TBR(mean) and TBR(max) were significantly higher at the later timepoint, as well as the SUV(max) of (68)Ga-PSMA-11. The highest %ID/g was determined in the kidneys (94.0 ± 13.6%ID/g 1 h p.i.) and the bladder (6.48 ± 2.18%ID/g 1 h p.i.). No significant increase in bone uptake was seen between 1 and 2 h p.i. Both radiotracers showed high affinity for the PSMA receptor. Over time, all uptake parameters were higher for (18)F-PSMA-11 compared to (68)Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late (18)F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of (18)F-PSMA-11 as well as no significant increase in bone uptake. Nature Publishing Group UK 2020-12-03 /pmc/articles/PMC7713063/ /pubmed/33273603 http://dx.doi.org/10.1038/s41598-020-78273-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Piron, Sarah
Verhoeven, Jeroen
Descamps, Benedicte
Kersemans, Ken
De Man, Kathia
Van Laeken, Nick
Pieters, Leen
Vral, Anne
Vanhove, Christian
De Vos, Filip
Intra-individual dynamic comparison of (18)F-PSMA-11 and (68)Ga-PSMA-11 in LNCaP xenograft bearing mice
title Intra-individual dynamic comparison of (18)F-PSMA-11 and (68)Ga-PSMA-11 in LNCaP xenograft bearing mice
title_full Intra-individual dynamic comparison of (18)F-PSMA-11 and (68)Ga-PSMA-11 in LNCaP xenograft bearing mice
title_fullStr Intra-individual dynamic comparison of (18)F-PSMA-11 and (68)Ga-PSMA-11 in LNCaP xenograft bearing mice
title_full_unstemmed Intra-individual dynamic comparison of (18)F-PSMA-11 and (68)Ga-PSMA-11 in LNCaP xenograft bearing mice
title_short Intra-individual dynamic comparison of (18)F-PSMA-11 and (68)Ga-PSMA-11 in LNCaP xenograft bearing mice
title_sort intra-individual dynamic comparison of (18)f-psma-11 and (68)ga-psma-11 in lncap xenograft bearing mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713063/
https://www.ncbi.nlm.nih.gov/pubmed/33273603
http://dx.doi.org/10.1038/s41598-020-78273-7
work_keys_str_mv AT pironsarah intraindividualdynamiccomparisonof18fpsma11and68gapsma11inlncapxenograftbearingmice
AT verhoevenjeroen intraindividualdynamiccomparisonof18fpsma11and68gapsma11inlncapxenograftbearingmice
AT descampsbenedicte intraindividualdynamiccomparisonof18fpsma11and68gapsma11inlncapxenograftbearingmice
AT kersemansken intraindividualdynamiccomparisonof18fpsma11and68gapsma11inlncapxenograftbearingmice
AT demankathia intraindividualdynamiccomparisonof18fpsma11and68gapsma11inlncapxenograftbearingmice
AT vanlaekennick intraindividualdynamiccomparisonof18fpsma11and68gapsma11inlncapxenograftbearingmice
AT pietersleen intraindividualdynamiccomparisonof18fpsma11and68gapsma11inlncapxenograftbearingmice
AT vralanne intraindividualdynamiccomparisonof18fpsma11and68gapsma11inlncapxenograftbearingmice
AT vanhovechristian intraindividualdynamiccomparisonof18fpsma11and68gapsma11inlncapxenograftbearingmice
AT devosfilip intraindividualdynamiccomparisonof18fpsma11and68gapsma11inlncapxenograftbearingmice