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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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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 |
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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 |
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