Abstract
Gastrin-releasing peptide receptors (GRPr) are a member of the bombesin (BBN) receptor family. GRPr are expressed in high numbers on specific human cancers, including human prostate cancer. Therefore, copper-64 ({sup 64}Cu) radiolabeled BBN(7-14)NH{sub 2} conjugates could have potential for diagnosis of human prostate cancer via positron-emission tomography (PET). The aim of this study was to produce [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}] conjugates for prostate cancer imaging, where X=pharmacokinetic modifier (beta-alanine, 5-aminovaleric acid, 6-aminohexanoic acid, 8-aminooctanoic acid, 9-aminonanoic acid or para-aminobenzoic acid) and NO2A=1,4,7-triazacyclononane-1,4-diacetic acid [a derivative of NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid)]. Methods: [(X)-BBN(7-14)NH{sub 2}] Conjugates were synthesized by solid-phase peptide synthesis (SPPS), after which NOTA was added via manual conjugation. The new peptide conjugates were radiolabeled with {sup 64}Cu radionuclide. The receptor-binding affinity was determined in human prostate PC-3 cells, and tumor-targeting efficacy was determined in PC-3 tumor-bearing severely combined immunodeficient (SCID) mice. Whole-body maximum intensity microPET/CT images of PC-3 tumor-bearing SCID mice were obtained 18 h postinjection (pi). Results: Competitive binding assays in PC-3 cells indicated high receptor-binding affinity for the [NO2A-(X)-BBN(7-14)NH{sub 2}] and [{sup nat}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}] conjugates. In vivo biodistribution studies of the [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}] conjugates at 1, 4 and 24 h pi showed very high uptake of the tracer
More>>
Lane, Stephanie R., E-mail: srlf36@mail.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States);
Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States);
Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)];
Nanda, Prasanta;
[1]
Rold, Tammy L;
[2]
Sieckman, Gary L;
[3]
Figueroa, Said D;
[1]
Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States)];
Hoffman, Timothy J;
[3]
The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States);
Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)];
Jurisson, Silvia S;
[4]
Smith, Charles J., E-mail: smithcj@health.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States);
Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States);
University of Missouri Research Reactor Center, University of Missouri-Columbia, Columbia, MO 65211 (United States);
The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)]
- Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)
- Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)
- Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States)
- Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)
Citation Formats
Lane, Stephanie R., E-mail: srlf36@mail.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States), Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)], Nanda, Prasanta, Rold, Tammy L, Sieckman, Gary L, Figueroa, Said D, Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States)], Hoffman, Timothy J, The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)], Jurisson, Silvia S, Smith, Charles J., E-mail: smithcj@health.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States), University of Missouri Research Reactor Center, University of Missouri-Columbia, Columbia, MO 65211 (United States), and The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)].
Optimization, biological evaluation and microPET imaging of copper-64-labeled bombesin agonists, [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}], in a prostate tumor xenografted mouse model.
United Kingdom: N. p.,
2010.
Web.
doi:10.1016/j.nucmedbio.2010.04.016.
Lane, Stephanie R., E-mail: srlf36@mail.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States), Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)], Nanda, Prasanta, Rold, Tammy L, Sieckman, Gary L, Figueroa, Said D, Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States)], Hoffman, Timothy J, The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)], Jurisson, Silvia S, Smith, Charles J., E-mail: smithcj@health.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States), University of Missouri Research Reactor Center, University of Missouri-Columbia, Columbia, MO 65211 (United States), & The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)].
Optimization, biological evaluation and microPET imaging of copper-64-labeled bombesin agonists, [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}], in a prostate tumor xenografted mouse model.
United Kingdom.
https://doi.org/10.1016/j.nucmedbio.2010.04.016
Lane, Stephanie R., E-mail: srlf36@mail.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States), Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)], Nanda, Prasanta, Rold, Tammy L, Sieckman, Gary L, Figueroa, Said D, Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States)], Hoffman, Timothy J, The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)], Jurisson, Silvia S, Smith, Charles J., E-mail: smithcj@health.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States), University of Missouri Research Reactor Center, University of Missouri-Columbia, Columbia, MO 65211 (United States), and The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)].
2010.
"Optimization, biological evaluation and microPET imaging of copper-64-labeled bombesin agonists, [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}], in a prostate tumor xenografted mouse model."
United Kingdom.
https://doi.org/10.1016/j.nucmedbio.2010.04.016.
@misc{etde_21417820,
title = {Optimization, biological evaluation and microPET imaging of copper-64-labeled bombesin agonists, [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}], in a prostate tumor xenografted mouse model}
author = {Lane, Stephanie R., E-mail: srlf36@mail.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States), Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)], Nanda, Prasanta, Rold, Tammy L, Sieckman, Gary L, Figueroa, Said D, Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States)], Hoffman, Timothy J, The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)], Jurisson, Silvia S, Smith, Charles J., E-mail: smithcj@health.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States), University of Missouri Research Reactor Center, University of Missouri-Columbia, Columbia, MO 65211 (United States), and The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)]}
abstractNote = {Gastrin-releasing peptide receptors (GRPr) are a member of the bombesin (BBN) receptor family. GRPr are expressed in high numbers on specific human cancers, including human prostate cancer. Therefore, copper-64 ({sup 64}Cu) radiolabeled BBN(7-14)NH{sub 2} conjugates could have potential for diagnosis of human prostate cancer via positron-emission tomography (PET). The aim of this study was to produce [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}] conjugates for prostate cancer imaging, where X=pharmacokinetic modifier (beta-alanine, 5-aminovaleric acid, 6-aminohexanoic acid, 8-aminooctanoic acid, 9-aminonanoic acid or para-aminobenzoic acid) and NO2A=1,4,7-triazacyclononane-1,4-diacetic acid [a derivative of NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid)]. Methods: [(X)-BBN(7-14)NH{sub 2}] Conjugates were synthesized by solid-phase peptide synthesis (SPPS), after which NOTA was added via manual conjugation. The new peptide conjugates were radiolabeled with {sup 64}Cu radionuclide. The receptor-binding affinity was determined in human prostate PC-3 cells, and tumor-targeting efficacy was determined in PC-3 tumor-bearing severely combined immunodeficient (SCID) mice. Whole-body maximum intensity microPET/CT images of PC-3 tumor-bearing SCID mice were obtained 18 h postinjection (pi). Results: Competitive binding assays in PC-3 cells indicated high receptor-binding affinity for the [NO2A-(X)-BBN(7-14)NH{sub 2}] and [{sup nat}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}] conjugates. In vivo biodistribution studies of the [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}] conjugates at 1, 4 and 24 h pi showed very high uptake of the tracer in GRPr-positive tissue with little accumulation and retention in nontarget tissues. High-quality, high-contrast microPET images were obtained, with xenografted tumors being clearly visible at 18 h pi. Conclusions: NO2A chelator sufficiently stabilizes copper(II) radiometal under in vivo conditions, producing conjugates with very high uptake and retention in targeted GRPr. Preclinical evaluation of these new peptide conjugates in tumor-bearing mice provides some impetus for clinical evaluation in human patients.}
doi = {10.1016/j.nucmedbio.2010.04.016}
journal = []
issue = {7}
volume = {37}
place = {United Kingdom}
year = {2010}
month = {Oct}
}
title = {Optimization, biological evaluation and microPET imaging of copper-64-labeled bombesin agonists, [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}], in a prostate tumor xenografted mouse model}
author = {Lane, Stephanie R., E-mail: srlf36@mail.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States), Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)], Nanda, Prasanta, Rold, Tammy L, Sieckman, Gary L, Figueroa, Said D, Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States)], Hoffman, Timothy J, The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Department of Chemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States)], Jurisson, Silvia S, Smith, Charles J., E-mail: smithcj@health.missouri.ed [Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States), Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States), University of Missouri Research Reactor Center, University of Missouri-Columbia, Columbia, MO 65211 (United States), and The Radiopharmaceutical Sciences Institute, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)]}
abstractNote = {Gastrin-releasing peptide receptors (GRPr) are a member of the bombesin (BBN) receptor family. GRPr are expressed in high numbers on specific human cancers, including human prostate cancer. Therefore, copper-64 ({sup 64}Cu) radiolabeled BBN(7-14)NH{sub 2} conjugates could have potential for diagnosis of human prostate cancer via positron-emission tomography (PET). The aim of this study was to produce [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}] conjugates for prostate cancer imaging, where X=pharmacokinetic modifier (beta-alanine, 5-aminovaleric acid, 6-aminohexanoic acid, 8-aminooctanoic acid, 9-aminonanoic acid or para-aminobenzoic acid) and NO2A=1,4,7-triazacyclononane-1,4-diacetic acid [a derivative of NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid)]. Methods: [(X)-BBN(7-14)NH{sub 2}] Conjugates were synthesized by solid-phase peptide synthesis (SPPS), after which NOTA was added via manual conjugation. The new peptide conjugates were radiolabeled with {sup 64}Cu radionuclide. The receptor-binding affinity was determined in human prostate PC-3 cells, and tumor-targeting efficacy was determined in PC-3 tumor-bearing severely combined immunodeficient (SCID) mice. Whole-body maximum intensity microPET/CT images of PC-3 tumor-bearing SCID mice were obtained 18 h postinjection (pi). Results: Competitive binding assays in PC-3 cells indicated high receptor-binding affinity for the [NO2A-(X)-BBN(7-14)NH{sub 2}] and [{sup nat}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}] conjugates. In vivo biodistribution studies of the [{sup 64}Cu-NO2A-(X)-BBN(7-14)NH{sub 2}] conjugates at 1, 4 and 24 h pi showed very high uptake of the tracer in GRPr-positive tissue with little accumulation and retention in nontarget tissues. High-quality, high-contrast microPET images were obtained, with xenografted tumors being clearly visible at 18 h pi. Conclusions: NO2A chelator sufficiently stabilizes copper(II) radiometal under in vivo conditions, producing conjugates with very high uptake and retention in targeted GRPr. Preclinical evaluation of these new peptide conjugates in tumor-bearing mice provides some impetus for clinical evaluation in human patients.}
doi = {10.1016/j.nucmedbio.2010.04.016}
journal = []
issue = {7}
volume = {37}
place = {United Kingdom}
year = {2010}
month = {Oct}
}