64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors

Publication Date:
2018-02-02
Publisher:
The Society of Nuclear Medicine (SNM)
Print ISSN:
0022-3123
Topics:
Medicine
Published by:
http://www.snm.org/
_version_ 1836398772636090368
autor Pyo, A., Yun, M., Kim, H. S., Kim, T.-Y., Lee, J.-j., Kim, J. Y., Lee, S., Kwon, S. Y., Bom, H.-S., Kim, H.-S., Kim, D.-Y., Min, J.-J.
beschreibung The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed nonantibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, 3 64 Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biologic characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies were synthesized with the chelators 2-( p -isothiocyanatobenzyl)-1,4,7-triazacyclononane- N,N',N,''- triacetic acid trihydrochloride ([ p -SCN-Bn]-NOTA), 2,2',2''-(10-(2-(2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DOTA- N -hydroxysuccinimide ester), or 1-( p -isothiocyanatobenzyl)diethylenetriamine pentaacetic acid trihydrochloride ([ p -SCN-Bn]-DTPA) in 1.0 M NaHCO 3 buffer (pH 9.2) for 24 h. Purified NOTA-, DOTA-, and DTPA-conjugated repebody were radiolabeled with 64 Cu in 0.1 M NH 4 OAc buffer (pH 5.5). To compare the EGFR-binding affinities of the repebodies, cellular uptake studies were performed with the human non–small cell lung cancer cell line H1650 (high expression of EGFR) and the human colon adenocarcinoma cell line SW620 (low expression of EGFR). Biodistribution and small-animal PET imaging studies were performed using H1650 tumor–bearing mice. Results: Radiochemical yields of the 64 Cu-labeled repebodies were approximately 70%–80%. Cellular uptake of the NOTA-, DOTA-, and DTPA-repebodies was over 4-fold higher in H1650 cells than in SW620 cells at 1 h. The 3 repebodies had accumulated specifically in H1650 tumor–bearing nude mice by 1 h after intravenous injection and were retained for over 24 h, as measured by the percentage injected dose per gram of tissue (%ID/g). Tumor uptake of all repebodies increased from 1 to 6 h (at 1 h, 6.28, 8.46, and 6.91 %ID/g for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 9.4, 8.28, and 10.1 %ID/g, respectively). H1650 tumors were clearly visible after injection of each repebody, with high tumor-to-background ratios (at 1 h, 3.43, 4.89, and 2.38 for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 3.05, 4.36, and 2.08; at 24 h, 3.81, 4.58, and 2.86). Conclusion: The 3 64 Cu-repebody complexes demonstrated specific and rapid uptake in EGFR-expressing tumors within 1 h and may have potential as novel EGFR imaging agents for PET.
citation_standardnr 6152264
datenlieferant ipn_articles
feed_id 9585
feed_publisher The Society of Nuclear Medicine (SNM)
feed_publisher_url http://www.snm.org/
insertion_date 2018-02-02
journalissn 0022-3123
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The Society of Nuclear Medicine (SNM)
quelle Journal of Nuclear Medicine
relation http://jnm.snmjournals.org/cgi/content/short/59/2/340?rss=1
search_space articles
shingle_author_1 Pyo, A., Yun, M., Kim, H. S., Kim, T.-Y., Lee, J.-j., Kim, J. Y., Lee, S., Kwon, S. Y., Bom, H.-S., Kim, H.-S., Kim, D.-Y., Min, J.-J.
shingle_author_2 Pyo, A., Yun, M., Kim, H. S., Kim, T.-Y., Lee, J.-j., Kim, J. Y., Lee, S., Kwon, S. Y., Bom, H.-S., Kim, H.-S., Kim, D.-Y., Min, J.-J.
shingle_author_3 Pyo, A., Yun, M., Kim, H. S., Kim, T.-Y., Lee, J.-j., Kim, J. Y., Lee, S., Kwon, S. Y., Bom, H.-S., Kim, H.-S., Kim, D.-Y., Min, J.-J.
shingle_author_4 Pyo, A., Yun, M., Kim, H. S., Kim, T.-Y., Lee, J.-j., Kim, J. Y., Lee, S., Kwon, S. Y., Bom, H.-S., Kim, H.-S., Kim, D.-Y., Min, J.-J.
shingle_catch_all_1 64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors
The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed nonantibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, 3 64 Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biologic characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies were synthesized with the chelators 2-( p -isothiocyanatobenzyl)-1,4,7-triazacyclononane- N,N',N,''- triacetic acid trihydrochloride ([ p -SCN-Bn]-NOTA), 2,2',2''-(10-(2-(2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DOTA- N -hydroxysuccinimide ester), or 1-( p -isothiocyanatobenzyl)diethylenetriamine pentaacetic acid trihydrochloride ([ p -SCN-Bn]-DTPA) in 1.0 M NaHCO 3 buffer (pH 9.2) for 24 h. Purified NOTA-, DOTA-, and DTPA-conjugated repebody were radiolabeled with 64 Cu in 0.1 M NH 4 OAc buffer (pH 5.5). To compare the EGFR-binding affinities of the repebodies, cellular uptake studies were performed with the human non–small cell lung cancer cell line H1650 (high expression of EGFR) and the human colon adenocarcinoma cell line SW620 (low expression of EGFR). Biodistribution and small-animal PET imaging studies were performed using H1650 tumor–bearing mice. Results: Radiochemical yields of the 64 Cu-labeled repebodies were approximately 70%–80%. Cellular uptake of the NOTA-, DOTA-, and DTPA-repebodies was over 4-fold higher in H1650 cells than in SW620 cells at 1 h. The 3 repebodies had accumulated specifically in H1650 tumor–bearing nude mice by 1 h after intravenous injection and were retained for over 24 h, as measured by the percentage injected dose per gram of tissue (%ID/g). Tumor uptake of all repebodies increased from 1 to 6 h (at 1 h, 6.28, 8.46, and 6.91 %ID/g for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 9.4, 8.28, and 10.1 %ID/g, respectively). H1650 tumors were clearly visible after injection of each repebody, with high tumor-to-background ratios (at 1 h, 3.43, 4.89, and 2.38 for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 3.05, 4.36, and 2.08; at 24 h, 3.81, 4.58, and 2.86). Conclusion: The 3 64 Cu-repebody complexes demonstrated specific and rapid uptake in EGFR-expressing tumors within 1 h and may have potential as novel EGFR imaging agents for PET.
Pyo, A., Yun, M., Kim, H. S., Kim, T.-Y., Lee, J.-j., Kim, J. Y., Lee, S., Kwon, S. Y., Bom, H.-S., Kim, H.-S., Kim, D.-Y., Min, J.-J.
The Society of Nuclear Medicine (SNM)
0022-3123
00223123
shingle_catch_all_2 64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors
The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed nonantibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, 3 64 Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biologic characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies were synthesized with the chelators 2-( p -isothiocyanatobenzyl)-1,4,7-triazacyclononane- N,N',N,''- triacetic acid trihydrochloride ([ p -SCN-Bn]-NOTA), 2,2',2''-(10-(2-(2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DOTA- N -hydroxysuccinimide ester), or 1-( p -isothiocyanatobenzyl)diethylenetriamine pentaacetic acid trihydrochloride ([ p -SCN-Bn]-DTPA) in 1.0 M NaHCO 3 buffer (pH 9.2) for 24 h. Purified NOTA-, DOTA-, and DTPA-conjugated repebody were radiolabeled with 64 Cu in 0.1 M NH 4 OAc buffer (pH 5.5). To compare the EGFR-binding affinities of the repebodies, cellular uptake studies were performed with the human non–small cell lung cancer cell line H1650 (high expression of EGFR) and the human colon adenocarcinoma cell line SW620 (low expression of EGFR). Biodistribution and small-animal PET imaging studies were performed using H1650 tumor–bearing mice. Results: Radiochemical yields of the 64 Cu-labeled repebodies were approximately 70%–80%. Cellular uptake of the NOTA-, DOTA-, and DTPA-repebodies was over 4-fold higher in H1650 cells than in SW620 cells at 1 h. The 3 repebodies had accumulated specifically in H1650 tumor–bearing nude mice by 1 h after intravenous injection and were retained for over 24 h, as measured by the percentage injected dose per gram of tissue (%ID/g). Tumor uptake of all repebodies increased from 1 to 6 h (at 1 h, 6.28, 8.46, and 6.91 %ID/g for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 9.4, 8.28, and 10.1 %ID/g, respectively). H1650 tumors were clearly visible after injection of each repebody, with high tumor-to-background ratios (at 1 h, 3.43, 4.89, and 2.38 for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 3.05, 4.36, and 2.08; at 24 h, 3.81, 4.58, and 2.86). Conclusion: The 3 64 Cu-repebody complexes demonstrated specific and rapid uptake in EGFR-expressing tumors within 1 h and may have potential as novel EGFR imaging agents for PET.
Pyo, A., Yun, M., Kim, H. S., Kim, T.-Y., Lee, J.-j., Kim, J. Y., Lee, S., Kwon, S. Y., Bom, H.-S., Kim, H.-S., Kim, D.-Y., Min, J.-J.
The Society of Nuclear Medicine (SNM)
0022-3123
00223123
shingle_catch_all_3 64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors
The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed nonantibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, 3 64 Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biologic characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies were synthesized with the chelators 2-( p -isothiocyanatobenzyl)-1,4,7-triazacyclononane- N,N',N,''- triacetic acid trihydrochloride ([ p -SCN-Bn]-NOTA), 2,2',2''-(10-(2-(2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DOTA- N -hydroxysuccinimide ester), or 1-( p -isothiocyanatobenzyl)diethylenetriamine pentaacetic acid trihydrochloride ([ p -SCN-Bn]-DTPA) in 1.0 M NaHCO 3 buffer (pH 9.2) for 24 h. Purified NOTA-, DOTA-, and DTPA-conjugated repebody were radiolabeled with 64 Cu in 0.1 M NH 4 OAc buffer (pH 5.5). To compare the EGFR-binding affinities of the repebodies, cellular uptake studies were performed with the human non–small cell lung cancer cell line H1650 (high expression of EGFR) and the human colon adenocarcinoma cell line SW620 (low expression of EGFR). Biodistribution and small-animal PET imaging studies were performed using H1650 tumor–bearing mice. Results: Radiochemical yields of the 64 Cu-labeled repebodies were approximately 70%–80%. Cellular uptake of the NOTA-, DOTA-, and DTPA-repebodies was over 4-fold higher in H1650 cells than in SW620 cells at 1 h. The 3 repebodies had accumulated specifically in H1650 tumor–bearing nude mice by 1 h after intravenous injection and were retained for over 24 h, as measured by the percentage injected dose per gram of tissue (%ID/g). Tumor uptake of all repebodies increased from 1 to 6 h (at 1 h, 6.28, 8.46, and 6.91 %ID/g for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 9.4, 8.28, and 10.1 %ID/g, respectively). H1650 tumors were clearly visible after injection of each repebody, with high tumor-to-background ratios (at 1 h, 3.43, 4.89, and 2.38 for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 3.05, 4.36, and 2.08; at 24 h, 3.81, 4.58, and 2.86). Conclusion: The 3 64 Cu-repebody complexes demonstrated specific and rapid uptake in EGFR-expressing tumors within 1 h and may have potential as novel EGFR imaging agents for PET.
Pyo, A., Yun, M., Kim, H. S., Kim, T.-Y., Lee, J.-j., Kim, J. Y., Lee, S., Kwon, S. Y., Bom, H.-S., Kim, H.-S., Kim, D.-Y., Min, J.-J.
The Society of Nuclear Medicine (SNM)
0022-3123
00223123
shingle_catch_all_4 64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors
The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed nonantibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, 3 64 Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biologic characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies were synthesized with the chelators 2-( p -isothiocyanatobenzyl)-1,4,7-triazacyclononane- N,N',N,''- triacetic acid trihydrochloride ([ p -SCN-Bn]-NOTA), 2,2',2''-(10-(2-(2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (DOTA- N -hydroxysuccinimide ester), or 1-( p -isothiocyanatobenzyl)diethylenetriamine pentaacetic acid trihydrochloride ([ p -SCN-Bn]-DTPA) in 1.0 M NaHCO 3 buffer (pH 9.2) for 24 h. Purified NOTA-, DOTA-, and DTPA-conjugated repebody were radiolabeled with 64 Cu in 0.1 M NH 4 OAc buffer (pH 5.5). To compare the EGFR-binding affinities of the repebodies, cellular uptake studies were performed with the human non–small cell lung cancer cell line H1650 (high expression of EGFR) and the human colon adenocarcinoma cell line SW620 (low expression of EGFR). Biodistribution and small-animal PET imaging studies were performed using H1650 tumor–bearing mice. Results: Radiochemical yields of the 64 Cu-labeled repebodies were approximately 70%–80%. Cellular uptake of the NOTA-, DOTA-, and DTPA-repebodies was over 4-fold higher in H1650 cells than in SW620 cells at 1 h. The 3 repebodies had accumulated specifically in H1650 tumor–bearing nude mice by 1 h after intravenous injection and were retained for over 24 h, as measured by the percentage injected dose per gram of tissue (%ID/g). Tumor uptake of all repebodies increased from 1 to 6 h (at 1 h, 6.28, 8.46, and 6.91 %ID/g for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 9.4, 8.28, and 10.1 %ID/g, respectively). H1650 tumors were clearly visible after injection of each repebody, with high tumor-to-background ratios (at 1 h, 3.43, 4.89, and 2.38 for NOTA-, DOTA-, and DTPA-repebody, respectively; at 6 h, 3.05, 4.36, and 2.08; at 24 h, 3.81, 4.58, and 2.86). Conclusion: The 3 64 Cu-repebody complexes demonstrated specific and rapid uptake in EGFR-expressing tumors within 1 h and may have potential as novel EGFR imaging agents for PET.
Pyo, A., Yun, M., Kim, H. S., Kim, T.-Y., Lee, J.-j., Kim, J. Y., Lee, S., Kwon, S. Y., Bom, H.-S., Kim, H.-S., Kim, D.-Y., Min, J.-J.
The Society of Nuclear Medicine (SNM)
0022-3123
00223123
shingle_title_1 64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors
shingle_title_2 64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors
shingle_title_3 64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors
shingle_title_4 64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors
timestamp 2025-06-30T23:32:23.779Z
titel 64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors
titel_suche 64Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors
topic WW-YZ
uid ipn_articles_6152264