| Online-Ressource |
Verfasst von: | Santos, José Carlos dos [VerfasserIn]  |
| Schäfer, Martin [VerfasserIn]  |
| Bauder-Wüst, Ulrike [VerfasserIn]  |
| Beijer, Barbro [VerfasserIn]  |
| Eder, Matthias [VerfasserIn]  |
| Leotta, Karin [VerfasserIn]  |
| Kleist, Christian [VerfasserIn]  |
| Meyer, Jan-Philip [VerfasserIn]  |
| Dilling, Thomas R. [VerfasserIn]  |
| Lewis, Jason S. [VerfasserIn]  |
| Kratochwil, Clemens [VerfasserIn]  |
| Kopka, Klaus [VerfasserIn]  |
| Haberkorn, Uwe [VerfasserIn]  |
| Mier, Walter [VerfasserIn]  |
Titel: | Refined chelator spacer moieties ameliorate the pharmacokinetics of PSMA-617 |
Verf.angabe: | José Carlos dos Santos, Martin Schäfer, Ulrike Bauder-Wüst, Barbro Beijer, Matthias Eder, Karin Leotta, Christian Kleist, Jan-Philip Meyer, Thomas R. Dilling, Jason S. Lewis, Clemens Kratochwil, Klaus Kopka, Uwe Haberkorn and Walter Mier |
E-Jahr: | 2022 |
Jahr: | 09 August 2022 |
Umfang: | 12 S. |
Fussnoten: | Gesehen am 03.11.2022 |
Titel Quelle: | Enthalten in: Frontiers in Chemistry |
Ort Quelle: | Lausanne : Frontiers Media, 2013 |
Jahr Quelle: | 2022 |
Band/Heft Quelle: | 10(2022), Artikel-ID 898692, Seite 1-12 |
ISSN Quelle: | 2296-2646 |
Abstract: | Prostate-specific membrane antigen (PSMA) binding tracers are promising agents for the targeting of prostate tumors. To further optimize the clinically established radiopharmaceutical PSMA-617, novel PSMA ligands for prostate cancer endoradiotherapy were developed. A series of PSMA binding tracers that comprise a benzyl group at the chelator moiety was obtained by solid-phase synthesis. The compounds were labeled with 68Ga or 177Lu. Competitive cell-binding assays and internalization assays were performed using the cell line C4-2, a subline of the PSMA positive cell line LNCaP (human lymph node carcinoma of the prostate). PET-imaging and biodistribution studies were conducted in a C4-2 tumor bearing BALB/c nu/nu mouse model. All 68Ga-labeled ligands were stable in human serum over 2 h; 177Lu-CA030 was stable over 72 h. The PSMA ligands revealed inhibition potencies [Ki] (equilibrium inhibition constants) between 4.8 and 33.8 nM. The percentage of internalization of the injected activity/106 cells of 68Ga-CA028, 68Ga-CA029 and 68Ga-CA030 was 41.2 ± 2.7, 44.3 ± 3.9 and 53.8 ± 5.4 respectively; for the comparator 68Ga-PSMA-617 15.5 ± 3.1 was determined. Small animal PET-imaging of the compounds showed a high tumor-to-background contrast. Organ distribution studies revealed high specific uptake in the tumor, i.e. approximately 34.4 ± 9.8 percentage of injected dose per gram (%ID/g) at 1 h post injection for 68Ga-CA028. At 1 h p.i. 68Ga-CA028 and 68Ga-CA030 demonstrated lower kidney uptake than 68Ga-PSMA-617, but at later time-points kidney time-activity-curves converge. In line with the preclinical data, first diagnostic PET imaging using 68Ga-CA028 and 68Ga-CA030 revealed high-contrast detection of bone and lymph node lesions in patients with metastatic prostate cancer. The novel PSMA ligands, in particular CA028 and CA030, are promising agents for targeting PSMA-positive tumor lesions as shown in the preclinical evaluation and in a first patient, respectively. Thus, clinical translation of 68Ga-CA028 and 68Ga/177Lu-CA030 for diagnostics and endoradiotherapy of prostate cancer in larger cohorts of patients is warranted. |
DOI: | doi:10.3389/fchem.2022.898692 |
URL: | kostenfrei: Volltext: https://doi.org/10.3389/fchem.2022.898692 |
| kostenfrei: Volltext: https://www.frontiersin.org/articles/10.3389/fchem.2022.898692/full |
| DOI: https://doi.org/10.3389/fchem.2022.898692 |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1820701417 |
Verknüpfungen: | → Zeitschrift |
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Lokale URL UB: | Zum Volltext |
Refined chelator spacer moieties ameliorate the pharmacokinetics of PSMA-617 / Santos, José Carlos dos [VerfasserIn]; 09 August 2022 (Online-Ressource)