Nuklearmedizin 2019; 58(02): 137
DOI: 10.1055/s-0039-1683565
Vorträge
Radiochemie und -pharmazie
Georg Thieme Verlag KG Stuttgart · New York

Discovery of F-18-JK-PSMA-7 as PET-probe suitable for imaging of small PSMA expressing lesions

BD Zlatopolskiy
1   Uniklinik Köln, Institut für Radiochemie und Experimentelle Molekulare Bildgebung (IREMB), Köln
,
H Endepols
1   Uniklinik Köln, Institut für Radiochemie und Experimentelle Molekulare Bildgebung (IREMB), Köln
,
P Krapf
2   Forschungszentrum Jülich, Institut für Neurowissenschaften und Medizin Nuklearchemie (INM-5), Jülich
,
M Guliyev
1   Uniklinik Köln, Institut für Radiochemie und Experimentelle Molekulare Bildgebung (IREMB), Köln
,
E Urusova
2   Forschungszentrum Jülich, Institut für Neurowissenschaften und Medizin Nuklearchemie (INM-5), Jülich
,
R Richarz
2   Forschungszentrum Jülich, Institut für Neurowissenschaften und Medizin Nuklearchemie (INM-5), Jülich
,
M Hohberg
3   Uniklinik Köln, Nuklearmedizin, Köln
,
M Dietlein
3   Uniklinik Köln, Nuklearmedizin, Köln
,
A Drzezga
3   Uniklinik Köln, Nuklearmedizin, Köln
,
B Neumaier
2   Forschungszentrum Jülich, Institut für Neurowissenschaften und Medizin Nuklearchemie (INM-5), Jülich
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
27. März 2019 (online)

 
 

    Ziel/Aim:

    The aim of this study was the development of F-18-labeled PSMA specific probes with improved PSMA sensitivity and imaging properties.

    Methodik/Methods:

    Eight potential PSMA ligands, with general structure HO-X(Y-F-18)-CO-Glu-OH were prepared. The cellular uptake of the candidates in PSMA+ LNCaP C4 – 2 and PSMA- PC-3 cells was compared to that of F-18-DCFPyL. Tracers were evaluated by µPET in normal rats employing PSMA+ peripheral ganglia as target structures mimicking small PCa lesions. For the best candidate the resulting PET scans were assessed in comparison to F-18-DCFPyL and F-18-PSMA-1007 scans with respect to key image quality parameters.

    Ergebnisse/Results:

    Radiofluorinated probes were produced in 20 – 40% RCYs and excellent radiochemical purities. HO-Glu{NH(CH2)2NH-6-F-18-Py}-CO-Glu-OH, F-18-Thia-DCFPyL and F-18 – 2-MeO-DCFPyL (F-18-JK-PSMA-7) demonstrated PSMA specific cellular uptake comparable or higher than that of F-18-DCFPyL (%ID/105 cells: 1.13 ± 0.03 and 3.20 ± 0.02; 1.21 ± 0.03 and 3.07 ± 0.02; and 2.03 ± 0.03 and 3.31 ± 0.01 vs. 1.55 ± 0.05 and 3.1 ± 0.03 after 2 and 4h incubation, respectively). While the signal-to-noise ratio of the F-18-Thia-DCFPyL, F-18-DCFPyL and F-18-PSMA-1007 were comparable (4.04, 6.4 ± 1.9 and 6.2 ± 1.9), it was higher for F-18-JK-PSMA-7 scans (8.2 ± 1.7). The image sharpness measured for the superior cervical ganglion was significantly higher for F-18-JK-PSMA-7 and F-18-PSMA-1007 compared to F-18-DCFPyL (0.075 ± 0.027 and 0.097 ± 0.025 vs. 0.019 ± 0.008). The image resolution determined for the apical pair of spinal ganglia was comparable for all three tracers (1.09 ± 0.04 and 0.92 ± 0.07 vs. 1.00 ± 0.14). F-18-PSMA-1007 demonstrated higher blood protein binding (%ID: 62.6 ± 10.7 vs. 12.9 ± 3.0 and 16.3 ± 4.2) and bone uptake than F-18-DCFPyL and F-18-PSMA-7 (%ID: 33.2 ± 9.5 vs. 12.4 ± 4.3 and 9.9 ± 1.9).

    Schlussfolgerungen/Conclusions:

    F-18-JK-PSMA-7 is a promising candidate for high quality visualization of small PSMA-positive lesions. Excellent preclinical imaging properties justify further preclinical and clinical studies of this tracer.


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