Radiolabeled B9958 Derivatives for Imaging Bradykinin B1 Receptor Expression with Positron Emission Tomography: Effect of the Radiolabel-Chelator Complex on Biodistribution and Tumor Uptake
hB1R and B1R-negative (B1R-) HEK293T tumors. Z02176 (Ga-DOTA-Pip-B9958; Pip: 4-amino-(1-carboxymethyl)piperidine), Z02137 (Ga-NODA-Mpaa-Pip-B9958; Mpaa: 4-methylphenylacetic acid), and Z04139 (AlF-NODA-Mpaa-Pip-B9958) bound hB1R with high affinity (Ki = 1.4-2.5 nM). (68)Ga-/(18)F-labeled peptides were obtained on average in ≥32% decay-corrected radiochemical yield with >99% radiochemical purity and 100-261 GBq/μmol specific activity. Biodistribution/imaging studies at 1 h postinjection showed that all tracers cleared rapidly from background tissues (except kidneys) and were excreted predominantly via the renal pathway. Only kidneys, bladders, and B1R+ tumors were clearly visualized in PET images. Uptake in B1R+ tumor was higher by using (68)Ga-Z02176 (28.9 ± 6.21 %ID/g) and (18)F-Z04139 (22.6 ± 3.41 %ID/g) than (68)Ga-Z02137 (14.0 ± 4.86 %ID/g). The B1R+ tumor-to-blood and B1R+ tumor-to-muscle contrast ratios were also higher for (68)Ga-Z02176 (56.1 ± 17.3 and 167 ± 57.6) and (18)F-Z04139 (58.0 ± 20.9 and 173 ± 42.9) than (68)Ga-Z02137 (34.3 ± 15.2 and 103 ± 30.2). With improved target-to-background contrast (68)Ga-Z02176 and (18)F-Z04139 are promising for imaging B1R expression in cancers with PET..
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2016 |
|---|---|
| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Molecular pharmaceutics - 13(2016), 8, Seite 2823 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhang, Zhengxing [VerfasserIn] |
|---|
| Links: |
|---|
| BKL: |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
OLC1980787050 |
|---|
| LEADER | 01000caa a2200265 4500 | ||
|---|---|---|---|
| 001 | OLC1980787050 | ||
| 003 | DE-627 | ||
| 005 | 20230517075915.0 | ||
| 007 | tu | ||
| 008 | 160816s2016 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a PQ20160815 |
| 035 | |a (DE-627)OLC1980787050 | ||
| 035 | |a (DE-599)GBVOLC1980787050 | ||
| 035 | |a (PRQ)pubmed_primary_273485170 | ||
| 035 | |a (KEY)0547757320160000013000802823radiolabeledb9958derivativesforimagingbradykininb1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 540 |a 610 |q DNB |
| 084 | |a PHARM |2 fid | ||
| 084 | |a 44.40 |2 bkl | ||
| 084 | |a 44.42 |2 bkl | ||
| 100 | 1 | |a Zhang, Zhengxing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Radiolabeled B9958 Derivatives for Imaging Bradykinin B1 Receptor Expression with Positron Emission Tomography: Effect of the Radiolabel-Chelator Complex on Biodistribution and Tumor Uptake |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 520 | |a Bradykinin B1 receptor (B1R), which is upregulated in a variety of malignancies, is an attractive cancer imaging biomarker. In this study we optimized the selection of radiolabel-chelator complex to improve tumor uptake and tumor-to-background contrast of radiolabeled analogues of B9958 (Lys-Lys-Arg-Pro-Hyp-Gly-Cpg-Ser-d-Tic-Cpg), a potent B1R antagonist. Peptide sequences were assembled on solid phase. Cold standards were prepared by incubating DOTA-/NODA-conjugated peptides with GaCl3, and by incubating AlOH-NODA-conjugated peptide with NaF. Binding affinities were measured via in vitro competition binding assays. (68)Ga and (18)F labeling experiments were performed in acidic buffer and purified by HPLC. Imaging/biodistribution studies were performed in mice bearing both B1R-positive (B1R+) HEK293T::hB1R and B1R-negative (B1R-) HEK293T tumors. Z02176 (Ga-DOTA-Pip-B9958; Pip: 4-amino-(1-carboxymethyl)piperidine), Z02137 (Ga-NODA-Mpaa-Pip-B9958; Mpaa: 4-methylphenylacetic acid), and Z04139 (AlF-NODA-Mpaa-Pip-B9958) bound hB1R with high affinity (Ki = 1.4-2.5 nM). (68)Ga-/(18)F-labeled peptides were obtained on average in ≥32% decay-corrected radiochemical yield with >99% radiochemical purity and 100-261 GBq/μmol specific activity. Biodistribution/imaging studies at 1 h postinjection showed that all tracers cleared rapidly from background tissues (except kidneys) and were excreted predominantly via the renal pathway. Only kidneys, bladders, and B1R+ tumors were clearly visualized in PET images. Uptake in B1R+ tumor was higher by using (68)Ga-Z02176 (28.9 ± 6.21 %ID/g) and (18)F-Z04139 (22.6 ± 3.41 %ID/g) than (68)Ga-Z02137 (14.0 ± 4.86 %ID/g). The B1R+ tumor-to-blood and B1R+ tumor-to-muscle contrast ratios were also higher for (68)Ga-Z02176 (56.1 ± 17.3 and 167 ± 57.6) and (18)F-Z04139 (58.0 ± 20.9 and 173 ± 42.9) than (68)Ga-Z02137 (34.3 ± 15.2 and 103 ± 30.2). With improved target-to-background contrast (68)Ga-Z02176 and (18)F-Z04139 are promising for imaging B1R expression in cancers with PET. | ||
| 700 | 1 | |a Amouroux, Guillaume |4 oth | |
| 700 | 1 | |a Pan, Jinhe |4 oth | |
| 700 | 1 | |a Jenni, Silvia |4 oth | |
| 700 | 1 | |a Zeisler, Jutta |4 oth | |
| 700 | 1 | |a Zhang, Chengcheng |4 oth | |
| 700 | 1 | |a Liu, Zhibo |4 oth | |
| 700 | 1 | |a Perrin, David M |4 oth | |
| 700 | 1 | |a Bénard, François |4 oth | |
| 700 | 1 | |a Lin, Kuo-Shyan |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular pharmaceutics |d Washington, DC : American Chemical Society, 2004 |g 13(2016), 8, Seite 2823 |w (DE-627)380768550 |w (DE-600)2138405-8 |w (DE-576)435513230 |x 1543-8384 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2016 |g number:8 |g pages:2823 |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/27348517 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a FID-PHARM | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a SSG-OLC-DE-84 | ||
| 912 | |a SSG-OPC-PHA | ||
| 912 | |a GBV_ILN_70 | ||
| 936 | b | k | |a 44.40 |q AVZ |
| 936 | b | k | |a 44.42 |q AVZ |
| 951 | |a AR | ||
| 952 | |d 13 |j 2016 |e 8 |h 2823 | ||