Refined chelator spacer moieties ameliorate the pharmacokinetics of PSMA-617
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 t...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
09 August 2022
|
| In: |
Frontiers in Chemistry
Year: 2022, Jahrgang: 10, Pages: 1-12 |
| ISSN: | 2296-2646 |
| DOI: | 10.3389/fchem.2022.898692 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fchem.2022.898692 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fchem.2022.898692/full 
|
| Verfasserangaben: | 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 |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1820701417 | ||
| 003 | DE-627 | ||
| 005 | 20250110004958.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 221103s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fchem.2022.898692 |2 doi | |
| 035 | |a (DE-627)1820701417 | ||
| 035 | |a (DE-599)KXP1820701417 | ||
| 035 | |a (OCoLC)1360438829 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Santos, José Carlos dos |d 1980- |e VerfasserIn |0 (DE-588)1187285749 |0 (DE-627)1666416495 |4 aut | |
| 245 | 1 | 0 | |a Refined chelator spacer moieties ameliorate the pharmacokinetics of PSMA-617 |c 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 |
| 264 | 1 | |c 09 August 2022 | |
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 03.11.2022 | ||
| 520 | |a 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. | ||
| 700 | 1 | |a Schäfer, Martin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bauder-Wüst, Ulrike |e VerfasserIn |4 aut | |
| 700 | 1 | |a Beijer, Barbro |e VerfasserIn |0 (DE-588)1058353705 |0 (DE-627)796731713 |0 (DE-576)186718780 |4 aut | |
| 700 | 1 | |8 1\p |a Eder, Matthias |d 1959- |e VerfasserIn |0 (DE-588)133667006 |0 (DE-627)550190856 |0 (DE-576)300011032 |4 aut | |
| 700 | 1 | |8 2\p |a Leotta, Karin |e VerfasserIn |0 (DE-588)1068657669 |0 (DE-627)82057404X |0 (DE-576)427989345 |4 aut | |
| 700 | 1 | |a Kleist, Christian |e VerfasserIn |0 (DE-588)138977410 |0 (DE-627)703170287 |0 (DE-576)309272971 |4 aut | |
| 700 | 1 | |a Meyer, Jan-Philip |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dilling, Thomas R. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lewis, Jason S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kratochwil, Clemens |d 1978- |e VerfasserIn |0 (DE-588)134026276 |0 (DE-627)559871686 |0 (DE-576)300262787 |4 aut | |
| 700 | 1 | |8 3\p |a Kopka, Klaus |d 1968- |e VerfasserIn |0 (DE-588)173031862 |0 (DE-627)69795661X |0 (DE-576)133884724 |4 aut | |
| 700 | 1 | |a Haberkorn, Uwe |d 1959- |e VerfasserIn |0 (DE-588)1022913905 |0 (DE-627)717331245 |0 (DE-576)366166352 |4 aut | |
| 700 | 1 | |a Mier, Walter |d 1966- |e VerfasserIn |0 (DE-588)12029026X |0 (DE-627)69653567X |0 (DE-576)292141599 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in Chemistry |d Lausanne : Frontiers Media, 2013 |g 10(2022), Artikel-ID 898692, Seite 1-12 |h Online-Ressource |w (DE-627)742224538 |w (DE-600)2711776-5 |w (DE-576)381275124 |x 2296-2646 |7 nnas |a Refined chelator spacer moieties ameliorate the pharmacokinetics of PSMA-617 |
| 773 | 1 | 8 | |g volume:10 |g year:2022 |g elocationid:898692 |g pages:1-12 |g extent:12 |a Refined chelator spacer moieties ameliorate the pharmacokinetics of PSMA-617 |
| 856 | 4 | 0 | |u https://doi.org/10.3389/fchem.2022.898692 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.frontiersin.org/articles/10.3389/fchem.2022.898692/full |x Verlag |z kostenfrei |3 Volltext |
| 883 | |8 1\p |a cgwrk |d 20241001 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 883 | |8 2\p |a cgwrk |d 20241001 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 883 | |8 3\p |a cgwrk |d 20241001 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 951 | |a AR | ||
| 992 | |a 20221103 | ||
| 993 | |a Article | ||
| 994 | |a 2022 | ||
| 998 | |g 12029026X |a Mier, Walter |m 12029026X:Mier, Walter |d 910000 |d 911400 |d 140000 |e 910000PM12029026X |e 911400PM12029026X |e 140000PM12029026X |k 0/910000/ |k 1/910000/911400/ |k 0/140000/ |p 14 |y j | ||
| 998 | |g 1022913905 |a Haberkorn, Uwe |m 1022913905:Haberkorn, Uwe |d 910000 |d 911400 |e 910000PH1022913905 |e 911400PH1022913905 |k 0/910000/ |k 1/910000/911400/ |p 13 | ||
| 998 | |g 134026276 |a Kratochwil, Clemens |m 134026276:Kratochwil, Clemens |d 910000 |d 911400 |e 910000PK134026276 |e 911400PK134026276 |k 0/910000/ |k 1/910000/911400/ |p 11 | ||
| 998 | |g 138977410 |a Kleist, Christian |m 138977410:Kleist, Christian |d 910000 |d 911400 |e 910000PK138977410 |e 911400PK138977410 |k 0/910000/ |k 1/910000/911400/ |p 7 | ||
| 998 | |g 1058353705 |a Beijer, Barbro |m 1058353705:Beijer, Barbro |d 910000 |d 911400 |e 910000PB1058353705 |e 911400PB1058353705 |k 0/910000/ |k 1/910000/911400/ |p 4 | ||
| 999 | |a KXP-PPN1820701417 |e 4206120048 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"eki":["1820701417"],"doi":["10.3389/fchem.2022.898692"]},"recId":"1820701417","relHost":[{"titleAlt":[{"title":"FCHEM"}],"part":{"pages":"1-12","volume":"10","extent":"12","year":"2022","text":"10(2022), Artikel-ID 898692, Seite 1-12"},"physDesc":[{"extent":"Online-Ressource"}],"disp":"Refined chelator spacer moieties ameliorate the pharmacokinetics of PSMA-617Frontiers in Chemistry","language":["eng"],"id":{"eki":["742224538"],"issn":["2296-2646"],"zdb":["2711776-5"]},"recId":"742224538","note":["Gesehen am 04.06.20"],"pubHistory":["2013 -"],"title":[{"title":"Frontiers in Chemistry","title_sort":"Frontiers in Chemistry"}],"origin":[{"publisher":"Frontiers Media","dateIssuedDisp":"2013-","publisherPlace":"Lausanne","dateIssuedKey":"2013"}],"type":{"bibl":"periodical","media":"Online-Ressource"}}],"name":{"displayForm":["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"]},"physDesc":[{"extent":"12 S."}],"language":["eng"],"title":[{"title":"Refined chelator spacer moieties ameliorate the pharmacokinetics of PSMA-617","title_sort":"Refined chelator spacer moieties ameliorate the pharmacokinetics of PSMA-617"}],"person":[{"display":"Santos, José Carlos dos","family":"Santos","given":"José Carlos dos","role":"aut"},{"role":"aut","given":"Martin","family":"Schäfer","display":"Schäfer, Martin"},{"role":"aut","given":"Ulrike","family":"Bauder-Wüst","display":"Bauder-Wüst, Ulrike"},{"role":"aut","display":"Beijer, Barbro","family":"Beijer","given":"Barbro"},{"role":"aut","display":"Eder, Matthias","given":"Matthias","family":"Eder"},{"display":"Leotta, Karin","family":"Leotta","given":"Karin","role":"aut"},{"display":"Kleist, Christian","given":"Christian","family":"Kleist","role":"aut"},{"role":"aut","display":"Meyer, Jan-Philip","given":"Jan-Philip","family":"Meyer"},{"given":"Thomas R.","family":"Dilling","display":"Dilling, Thomas R.","role":"aut"},{"display":"Lewis, Jason S.","family":"Lewis","given":"Jason S.","role":"aut"},{"role":"aut","family":"Kratochwil","given":"Clemens","display":"Kratochwil, Clemens"},{"given":"Klaus","family":"Kopka","display":"Kopka, Klaus","role":"aut"},{"role":"aut","display":"Haberkorn, Uwe","given":"Uwe","family":"Haberkorn"},{"role":"aut","given":"Walter","family":"Mier","display":"Mier, Walter"}],"origin":[{"dateIssuedKey":"2022","dateIssuedDisp":"09 August 2022"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"note":["Gesehen am 03.11.2022"]} | ||
| SRT | |a SANTOSJOSEREFINEDCHE0920 | ||