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 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.