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Intra-individual dynamic comparison of F-PSMA-11 and Ga-PSMA-11 in LNCaP xenograft bearing mice. | LitMetric

AI Article Synopsis

Article Abstract

Recently, a F-labeled derivative of the widely used Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although 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 F-PSMA-11 or 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 F-PSMA-11 and Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as ± 15 MBq F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUV, SUV, TBR and TBR). Mice underwent ex vivo biodistribution where 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) of F-PSMA-11 and 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 F-PSMA-11 and Ga-PSMA-11, while no difference was found for F-FDG uptake (except for SUV). Tumor uptake of F-PSMA-11 showed a similar trend over time as 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 and TBR were significantly higher at the later timepoint, as well as the SUV of 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 F-PSMA-11 compared to Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of F-PSMA-11 as well as no significant increase in bone uptake.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713063PMC
http://dx.doi.org/10.1038/s41598-020-78273-7DOI Listing

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