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Synthesis and preclinical evaluation of novel 18F-labeled Glu-urea-Glu-based PSMA inhibitors for prostate cancer imaging: a comparison with 18F-DCFPyl and 18F-PSMA-1007

Overview of attention for article published in EJNMMI Research, April 2018
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (64th percentile)
  • Good Attention Score compared to outputs of the same age and source (66th percentile)

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2 X users
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Citations

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35 Dimensions

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69 Mendeley
Title
Synthesis and preclinical evaluation of novel 18F-labeled Glu-urea-Glu-based PSMA inhibitors for prostate cancer imaging: a comparison with 18F-DCFPyl and 18F-PSMA-1007
Published in
EJNMMI Research, April 2018
DOI 10.1186/s13550-018-0382-8
Pubmed ID
Authors

Stephanie Robu, Alexander Schmidt, Matthias Eiber, Margret Schottelius, Thomas Günther, Behrooz Hooshyar Yousefi, Markus Schwaiger, Hans-Jürgen Wester

Abstract

Due to its high and consistent expression in prostate cancer (PCa), the prostate-specific membrane antigen (PSMA) represents an ideal target for molecular imaging and targeted therapy using highly specific radiolabeled PSMA ligands. To address the continuously growing clinical demand for 18F-labeled PSMA-probes, we developed two novel Glu-urea-Glu-(EuE)-based inhibitors, EuE-k-18F-FBOA (1) and EuE-k-β-a-18F-FPyl (2), both with optimized linker structure and different 18F-labeled aromatic moieties. The inhibitors were evaluated in a comparative preclinical study with 18F-DCFPyl and 18F-PSMA-1007. Radiolabeling procedures allowed preparation of (1) and (2) with high radiochemical yields (67 ± 7 and 53 ± 7%, d.c.) and purity (> 98%). When compared with 18F-DCFPyl (IC50 = 12.3 ± 1.2 nM) and 18F-PSMA-1007 (IC50 = 4.2 ± 0.5 nM), both metabolically stable EuE-based ligands showed commensurable or higher PSMA affinity (IC50 = 4.2 ± 0.4 nM (1), IC50 = 1.1 ± 0.2 nM (2)). Moreover, 1.4- and 2.7-fold higher internalization rates were observed for (1) and (2), respectively, resulting in markedly enhanced tumor accumulation in LNCaP-tumor-bearing mice ((1) 12.7 ± 2.0% IA/g, (2) 13.0° ± 1.0% IA/g vs. 7.3 ± 1.0% IA/g (18F-DCFPyl), 7.1 ± 1.5% IA/g (18F-PSMA-1007), 1 h p.i.). In contrast to (1), (2) showed higher kidney accumulation and delayed clearance kinetics. Due to the high hydrophilicity of both compounds, almost no unspecific uptake in non-target tissue was observed. In contrast, due to the less hydrophilic character (logP = - 1.6) and high plasma protein binding (98%), 18F-PSMA-1007 showed uptake in non-target tissue and predominantly hepatobiliary excretion, whereas, 18F-DCFPyl exhibited pharmacokinetics quite similar to those obtained with (1) and (2). Both 18F-labeled EuE-based PSMA ligands showed excellent in vitro and in vivo PSMA-targeting characteristics. The substantially higher tumor accumulation in mice compared to recently introduced 18F-PSMA-1007 and 18F-DCFPyl suggests their high value for preclinical studies investigating the effects on PSMA-expression. In contrast to (2), (1) seems to be more promising for further investigation, due to the more reliable 18F-labeling procedure, the faster clearance kinetics with comparable high tumor uptake, resulting therefore in better high-contrast microPET imaging as early as 1 h p.i.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 69 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 69 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 19%
Student > Bachelor 9 13%
Student > Master 7 10%
Student > Ph. D. Student 7 10%
Student > Doctoral Student 3 4%
Other 6 9%
Unknown 24 35%
Readers by discipline Count As %
Medicine and Dentistry 13 19%
Chemistry 10 14%
Pharmacology, Toxicology and Pharmaceutical Science 7 10%
Immunology and Microbiology 1 1%
Economics, Econometrics and Finance 1 1%
Other 9 13%
Unknown 28 41%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 April 2020.
All research outputs
#6,499,677
of 23,043,346 outputs
Outputs from EJNMMI Research
#116
of 564 outputs
Outputs of similar age
#115,041
of 329,221 outputs
Outputs of similar age from EJNMMI Research
#4
of 12 outputs
Altmetric has tracked 23,043,346 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 564 research outputs from this source. They receive a mean Attention Score of 2.5. This one has done well, scoring higher than 77% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 329,221 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.
We're also able to compare this research output to 12 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.