Synthesis and evaluation of a multifunctional probe with a high affinity for prostate-specific membrane antigen (PSMA) and bone
Prostate cancer frequently metastasizes to the bone. Because patients with bone metastases suffer from skeletal-related events, the diagnosis and treatment of bone metastases in the early stage are important. In this study, to improve the sensitivity of detecting bone metastases in patients with pro...
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| Veröffentlicht in: | Nuclear medicine and biology 2022-11, Vol.114-115, p.34-41 |
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| creator | Hirata, Saki Mishiro, Kenji Higashi, Takuma Fuchigami, Takeshi Munekane, Masayuki Arano, Yasushi Kinuya, Seigo Ogawa, Kazuma |
| description | Prostate cancer frequently metastasizes to the bone. Because patients with bone metastases suffer from skeletal-related events, the diagnosis and treatment of bone metastases in the early stage are important. In this study, to improve the sensitivity of detecting bone metastases in patients with prostate cancer, we designed, synthesized, and evaluated a multifunctional radiotracer, [67Ga]Ga-D11-PSMA-617 ([67Ga]3), with an undeca-aspartic acid as a bone-seeking moiety between [67Ga]Ga-DOTA and a prostate-specific membrane antigen (PSMA) ligand based on the lysine-urea-glutamate motif. [67Ga]3 showed a high affinity for hydroxyapatite and high uptake in PSMA-positive LNCaP cells. Moreover, in biodistribution experiments using tumor-bearing mice, [67Ga]3 exhibited high accumulation in the bone and PSMA-positive tumor although the accumulation of [67Ga]3 in the PSMA-positive tumor was lower than that of [67Ga]Ga-PSMA-617. This study provides valuable information for developing radiotheranostic probes combining multiple carriers with different mechanisms.
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| doi_str_mv | 10.1016/j.nucmedbio.2022.08.004 |
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[Display omitted]</description><subject>Accumulation</subject><subject>Affinity</subject><subject>Animals</subject><subject>Antigens</subject><subject>Aspartic acid</subject><subject>Bone cancer</subject><subject>Bone metastases</subject><subject>Bone Neoplasms - secondary</subject><subject>Bone tumors</subject><subject>Cell Line, Tumor</subject><subject>Gallium Radioisotopes</subject><subject>Glutamate Carboxypeptidase II - metabolism</subject><subject>Humans</subject><subject>Hydroxyapatite</subject><subject>Lysine</subject><subject>Male</subject><subject>Membranes</subject><subject>Metastases</subject><subject>Mice</subject><subject>Positron Emission Tomography Computed Tomography</subject><subject>Positron-Emission Tomography</subject><subject>Prostate - metabolism</subject><subject>Prostate - pathology</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - diagnostic imaging</subject><subject>Prostatic Neoplasms - pathology</subject><subject>PSMA</subject><subject>Radioactive tracers</subject><subject>Radiotheranostics</subject><subject>Tissue Distribution</subject><subject>Tumors</subject><subject>Urea</subject><issn>0969-8051</issn><issn>1872-9614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1ERbeFvwCWuLSHhLHjZO3jquJLKmqlwtlynHHXq8RZYqdoT_x1nG7pgQunkWaed75eQt4xKBmw5sOuDLMdsGv9WHLgvARZAogXZMXkmheqYeIlWYFqVCGhZqfkLMYdZKVg8IqcVg1IKdf1ivy-O4S0xegjNaGj-GD62SQ_Bjo6augw98m7OdglZXq6n8YW6S-ftrm49fc5OOeDTwfqxmkpx2QSFnGP1jtv6YBDO5mAuXvy9xjoxe3dt83l47B2DPianDjTR3zzFM_Jj08fv199Ka5vPn-92lwXViieiloyC1YKFJxVbSeVrUXnOBjH2s5AZ1glsJG1rdBwyV1TGwMVByGM4k0nqnNyceybV_w5Y0x68NFi3-fdxjlqvmZVBbJWTUbf_4PuxnnK1y9Uk59dS6UytT5SNt8cJ3R6P_nBTAfNQC8e6Z1-9kgvHmmQOnuUlW-f-s9tLj_r_pqSgc0RwPyQB4-TjtZjsNj5CW3S3ej_O-QPWiOnlA</recordid><startdate>20221101</startdate><enddate>20221101</enddate><creator>Hirata, Saki</creator><creator>Mishiro, Kenji</creator><creator>Higashi, Takuma</creator><creator>Fuchigami, Takeshi</creator><creator>Munekane, Masayuki</creator><creator>Arano, Yasushi</creator><creator>Kinuya, Seigo</creator><creator>Ogawa, Kazuma</creator><general>Elsevier Inc</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20221101</creationdate><title>Synthesis and evaluation of a multifunctional probe with a high affinity for prostate-specific membrane antigen (PSMA) and bone</title><author>Hirata, Saki ; Mishiro, Kenji ; Higashi, Takuma ; Fuchigami, Takeshi ; Munekane, Masayuki ; Arano, Yasushi ; Kinuya, Seigo ; Ogawa, Kazuma</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-581c0c84e4213bd89c54df20af1bda0da134e685c3ea282f65aa032044a926d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Accumulation</topic><topic>Affinity</topic><topic>Animals</topic><topic>Antigens</topic><topic>Aspartic acid</topic><topic>Bone cancer</topic><topic>Bone metastases</topic><topic>Bone Neoplasms - secondary</topic><topic>Bone tumors</topic><topic>Cell Line, Tumor</topic><topic>Gallium Radioisotopes</topic><topic>Glutamate Carboxypeptidase II - metabolism</topic><topic>Humans</topic><topic>Hydroxyapatite</topic><topic>Lysine</topic><topic>Male</topic><topic>Membranes</topic><topic>Metastases</topic><topic>Mice</topic><topic>Positron Emission Tomography Computed Tomography</topic><topic>Positron-Emission Tomography</topic><topic>Prostate - metabolism</topic><topic>Prostate - pathology</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - diagnostic imaging</topic><topic>Prostatic Neoplasms - pathology</topic><topic>PSMA</topic><topic>Radioactive tracers</topic><topic>Radiotheranostics</topic><topic>Tissue Distribution</topic><topic>Tumors</topic><topic>Urea</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hirata, Saki</creatorcontrib><creatorcontrib>Mishiro, Kenji</creatorcontrib><creatorcontrib>Higashi, Takuma</creatorcontrib><creatorcontrib>Fuchigami, Takeshi</creatorcontrib><creatorcontrib>Munekane, Masayuki</creatorcontrib><creatorcontrib>Arano, Yasushi</creatorcontrib><creatorcontrib>Kinuya, Seigo</creatorcontrib><creatorcontrib>Ogawa, Kazuma</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nuclear medicine and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hirata, Saki</au><au>Mishiro, Kenji</au><au>Higashi, Takuma</au><au>Fuchigami, Takeshi</au><au>Munekane, Masayuki</au><au>Arano, Yasushi</au><au>Kinuya, Seigo</au><au>Ogawa, Kazuma</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and evaluation of a multifunctional probe with a high affinity for prostate-specific membrane antigen (PSMA) and bone</atitle><jtitle>Nuclear medicine and biology</jtitle><addtitle>Nucl Med Biol</addtitle><date>2022-11-01</date><risdate>2022</risdate><volume>114-115</volume><spage>34</spage><epage>41</epage><pages>34-41</pages><issn>0969-8051</issn><eissn>1872-9614</eissn><abstract>Prostate cancer frequently metastasizes to the bone. Because patients with bone metastases suffer from skeletal-related events, the diagnosis and treatment of bone metastases in the early stage are important. In this study, to improve the sensitivity of detecting bone metastases in patients with prostate cancer, we designed, synthesized, and evaluated a multifunctional radiotracer, [67Ga]Ga-D11-PSMA-617 ([67Ga]3), with an undeca-aspartic acid as a bone-seeking moiety between [67Ga]Ga-DOTA and a prostate-specific membrane antigen (PSMA) ligand based on the lysine-urea-glutamate motif. [67Ga]3 showed a high affinity for hydroxyapatite and high uptake in PSMA-positive LNCaP cells. Moreover, in biodistribution experiments using tumor-bearing mice, [67Ga]3 exhibited high accumulation in the bone and PSMA-positive tumor although the accumulation of [67Ga]3 in the PSMA-positive tumor was lower than that of [67Ga]Ga-PSMA-617. This study provides valuable information for developing radiotheranostic probes combining multiple carriers with different mechanisms.
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| subjects | Accumulation Affinity Animals Antigens Aspartic acid Bone cancer Bone metastases Bone Neoplasms - secondary Bone tumors Cell Line, Tumor Gallium Radioisotopes Glutamate Carboxypeptidase II - metabolism Humans Hydroxyapatite Lysine Male Membranes Metastases Mice Positron Emission Tomography Computed Tomography Positron-Emission Tomography Prostate - metabolism Prostate - pathology Prostate cancer Prostatic Neoplasms - diagnostic imaging Prostatic Neoplasms - pathology PSMA Radioactive tracers Radiotheranostics Tissue Distribution Tumors Urea |
| title | Synthesis and evaluation of a multifunctional probe with a high affinity for prostate-specific membrane antigen (PSMA) and bone |
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