Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice
Sarah Piron, Jeroen Verhoeven, Benedicte Descamps, Ken Kersemans, Kathia De Man, Nick Van Laeken, Leen Pieters, Anne Vral, Christian Vanhove, Filip De Vos
Abstract
Abstract 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.