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The aim was to compare the prostate-specific membrane antigen (PSMA)-targeting characteristics of PSMA-11, radiolabeled on the basis of chelation of 18 F-AlF, with those of 68 Ga-PSMA-11 to image PSMA-expressing xenografts. Methods: Labeling of 18 F-AlF-PSMA-11 via 18 F-AlF-complexation was performed as described by Boschi et al. and Malik et al. with minor modifications. Several conditions for the quality control of the labeling of 18 F-AlF-PSMA-11 via 18 F-AlF-complexation were evaluated to characterize the influence of ethanol, acetonitrile, and trifluoroacetic acid on the stability of the labeled product. Internalization kinetics of 18 F-AlF-PSMA-11 were compared with those of 68 Ga-PSMA-11 using PSMA-expressing LNCaP tumor cells. Biodistribution of 18 F-AlF-PSMA-11 (0.26 nmol/mouse, 8-9 MBq/mouse) in male BALB/c nude mice with PSMA-expressing subcutaneous LS174T-PSMA tumors was compared with that of 68 Ga-PSMA-11 at 1 and 2 h after injection. In addition, 18 F-AlF-PSMA-11 PET/CT and 68 Ga-PSMA-11 PET/CT imaging were performed at 1 and 2 h after injection. Results: In contrast to 68 Ga-PSMA-11, 18 F-AlF-PSMA-11 was not stable in water (radiochemical purity was 64.5% immediately after purification and 52.7% at 120 min after purification). 18 F-AlF-PSMA-11 remained relatively stable in 25 mM NH 4 OAc, pH 6.9, and radiochemical purity decreased from 98.5% at purification to 96.3%, 94.7%, and 92.5% at 60, 120, and 180 min after purification. In vitro, the 18 F- and 68 Ga-labeled compounds showed rapid internalization in LS174T-PSMA cells. The highest tumor uptake (percentage injected dose [%ID]) was observed at 2 h after injection (10.8 ± 2.3 %ID/g and 7.9 ± 1.3 %ID/g for 18 F-AlF-PSMA-11 and 68 Ga-PSMA-11, respectively [ P &gt; 0.05]). Renal tracer uptake peaked at 2 h after injection (43.5 ± 5.7 %ID/g and 105.8 ± 13.8 %ID/g for 18 F-AlF-PSMA-11 and 68 Ga-PSMA-11, respectively, P &lt; 0.05). Bone uptake of 18 F-AlF-PSMA-11 was 3.3 ± 0.6 at 1 h after injection and 5.0 ± 0.6 %ID/g at 2 h after injection and was dependent on the radiochemical purity at the time of injection. Bone uptake of 68 Ga-PSMA-11 reached 0.1 ± 0.0 %ID/g at 1 and 2 h after injection. PSMA-expressing xenografts could be visualized using both 68 Ga-PSMA-11- and 18 F-AlF-PSMA-11 PET/CT. Conclusion:  18 F-AlF-PSMA-11 using direct labeling with aluminum fluoride can be produced in NH 4 OAc, pH 6.9; shows a high internalization rate; and visualizes PSMA-expressing tumors with similar tumor uptake. Lower kidney uptake than with 68 Ga-PSMA-11 may be advantageous for tumor detection. However, the limited instability and consequent Al 18 F uptake in bone might hamper the visualization of small PCa bone metastases.

In Vitro and In Vivo Characterization of an 18F-AlF-Labeled PSMA Ligand for Imaging of PSMA-Expressing Xenografts

In Vitro and In Vivo Characterization of an ¹⁸F-AlF-Labeled PSMA Ligand for Imaging of PSMA-Expressing Xenografts