| Autor: |
Bibika M; Molecular Radiopharmacy, INRaSTES, NCSR 'Demokritos', 15341 Athens, Greece., Kanellopoulos P; Molecular Radiopharmacy, INRaSTES, NCSR 'Demokritos', 15341 Athens, Greece., Rouchota M; BIOEMTECH, Lefkippos Attica Technology Park NCSR 'Demokritos', 15310 Athens, Greece., Loudos G; BIOEMTECH, Lefkippos Attica Technology Park NCSR 'Demokritos', 15310 Athens, Greece., Nock BA; Molecular Radiopharmacy, INRaSTES, NCSR 'Demokritos', 15341 Athens, Greece., Krenning EP; Cyclotron Rotterdam BV, Erasmus MC, 3015 CE Rotterdam, The Netherlands., Maina T; Molecular Radiopharmacy, INRaSTES, NCSR 'Demokritos', 15341 Athens, Greece. |
| Abstrakt: |
Background: The concept of radiotheranostics relies on the overexpression of a biomolecular target on malignant cells to direct diagnostic/therapeutic radionuclide-carriers specifically to cancer lesions. The concomitant expression of more than one target in pathological lesions may be elegantly exploited to improve diagnostic sensitivity and therapeutic efficacy. Toward this goal, we explored a first example of a combined application of [ 99m Tc]Tc-DT11 (DT11, N 4 -Lys(MPBA-PEG4)-Arg-Arg-Pro-Tyr-Ile-Leu-OH; NTS 1 R-specific) and [ 99m Tc]Tc-DB7(DB7, N 4 -PEG2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; GRPR-specific) in prostate cancer models. Methods: Accordingly, the behavior of [ 99m Tc]Tc-DT11 was compared with that of the [ 99m Tc]Tc-DT11+[ 99m Tc]Tc-DB7 mixture in prostate adenocarcinoma PC-3 cells and xenografts in mice. The impact of stabilizing both radiotracers by Entresto ® , as a source of the potent neprilysin inhibitor sacubitrilat, was also investigated. Results: The PC-3 cell binding of the [ 99m Tc]Tc-DT11+[ 99m Tc]Tc-DB7 mixture surpassed that of [ 99m Tc]Tc-DT11. Likewise, the PC-3 tumor uptake of the [ 99m Tc]Tc-DT11+[ 99m Tc]Tc-DB7 mixture at 4 h post-injection was superior (7.70 ± 0.89%IA/g) compared with [ 99m Tc]Tc-DT11 (4.23 ± 0.58%IA/g; p < 0.0001). Treatment with Entresto ® led to further enhancement of the tumor uptake (to 11.57 ± 1.92%IA/g; p < 0.0001). Conclusions: In conclusion, this first preclinical study on prostate cancer models revealed clear advantages of dual NTS 1 R/GRPR targeting, justifying further assessment of this promising concept in other cancer models. |
