Imageological/Structural Study regarding the Improved Pharmacokinetics by 68 Ga-Labeled PEGylated PSMA Multimer in Prostate Cancer
PMSA (prostate-specific membrane antigen) is currently the most significant target for diagnosing and treating PCa (prostate cancer). Herein, we reported a series Ga/ Lu-labeled multimer PSMA tracer conjugating with PEG chain, including [ Ga]Ga-DOTA-(1P-PEG ), [ Ga]Ga-DOTA-(2P-PEG ), [ Ga]Ga-DOTA-(2...
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creator | Zhang, Huihui Rao, Maohua Zhao, Huayi Ren, Jianli Hao, Lan Zhong, Meng Chen, Yue Yang, Xia Feng, Yue Yuan, Gengbiao |
description | PMSA (prostate-specific membrane antigen) is currently the most significant target for diagnosing and treating PCa (prostate cancer). Herein, we reported a series
Ga/
Lu-labeled multimer PSMA tracer conjugating with PEG chain, including [
Ga]Ga-DOTA-(1P-PEG
), [
Ga]Ga-DOTA-(2P-PEG
), [
Ga]Ga-DOTA-(2P-PEG
), and [
Ga]Ga/[
Lu]Lu-DOTA-(2P-PEG
)
, which showed an advantage of a multivalent effect and PEGylation to achieve higher tumor accumulation and faster kidney clearance. To figure out how structural optimizations based on a PSMA multimer and PEGylation influence the probe's tumor-targeting ability, biodistribution, and metabolism, we examined PSMA molecular probes' affinities to PC-3 PIP (PSMA-highly-expressed PC-3 cell line), and conducted pharmacokinetics analysis, biodistribution detection, small animal PET/CT, and SPECT/CT imaging. The results showed that PEG
and PSMA dimer optimizations enhanced the probes' tumor-targeting ability in PC-3 PIP tumor-bearing mice models. Compared with the PSMA monomer, the PEGylated PSMA dimer reduced the elimination half-life in the blood and increased uptake in the tumor, and the biodistribution results were consistent with PET/CT imaging results. [
Ga]Ga-DOTA-(2P-PEG
)
exhibited higher tumor-to-organ ratios. When labeled by lutetium-177, relatively high accumulation of DOTA-(2P-PEG
)
was still detected in PC-3 PIP tumor-bearing mice models after 48 h, indicating its prolonged tumor retention time. Given the superiority in imaging, simple synthetic processes, and structural stability, DOTA-(2P-PEG
)
is expected to be a promising tumor-targeting diagnostic molecular probe in future clinical practice. |
format | Article |
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Ga/
Lu-labeled multimer PSMA tracer conjugating with PEG chain, including [
Ga]Ga-DOTA-(1P-PEG
), [
Ga]Ga-DOTA-(2P-PEG
), [
Ga]Ga-DOTA-(2P-PEG
), and [
Ga]Ga/[
Lu]Lu-DOTA-(2P-PEG
)
, which showed an advantage of a multivalent effect and PEGylation to achieve higher tumor accumulation and faster kidney clearance. To figure out how structural optimizations based on a PSMA multimer and PEGylation influence the probe's tumor-targeting ability, biodistribution, and metabolism, we examined PSMA molecular probes' affinities to PC-3 PIP (PSMA-highly-expressed PC-3 cell line), and conducted pharmacokinetics analysis, biodistribution detection, small animal PET/CT, and SPECT/CT imaging. The results showed that PEG
and PSMA dimer optimizations enhanced the probes' tumor-targeting ability in PC-3 PIP tumor-bearing mice models. Compared with the PSMA monomer, the PEGylated PSMA dimer reduced the elimination half-life in the blood and increased uptake in the tumor, and the biodistribution results were consistent with PET/CT imaging results. [
Ga]Ga-DOTA-(2P-PEG
)
exhibited higher tumor-to-organ ratios. When labeled by lutetium-177, relatively high accumulation of DOTA-(2P-PEG
)
was still detected in PC-3 PIP tumor-bearing mice models after 48 h, indicating its prolonged tumor retention time. Given the superiority in imaging, simple synthetic processes, and structural stability, DOTA-(2P-PEG
)
is expected to be a promising tumor-targeting diagnostic molecular probe in future clinical practice.</description><identifier>ISSN: 1424-8247</identifier><identifier>EISSN: 1424-8247</identifier><identifier>PMID: 37111347</identifier><language>eng</language><publisher>Switzerland</publisher><ispartof>Pharmaceuticals (Basel, Switzerland), 2023-04, Vol.16 (4)</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-5622-0016 ; 0000-0003-4088-7649</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37111347$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Huihui</creatorcontrib><creatorcontrib>Rao, Maohua</creatorcontrib><creatorcontrib>Zhao, Huayi</creatorcontrib><creatorcontrib>Ren, Jianli</creatorcontrib><creatorcontrib>Hao, Lan</creatorcontrib><creatorcontrib>Zhong, Meng</creatorcontrib><creatorcontrib>Chen, Yue</creatorcontrib><creatorcontrib>Yang, Xia</creatorcontrib><creatorcontrib>Feng, Yue</creatorcontrib><creatorcontrib>Yuan, Gengbiao</creatorcontrib><title>Imageological/Structural Study regarding the Improved Pharmacokinetics by 68 Ga-Labeled PEGylated PSMA Multimer in Prostate Cancer</title><title>Pharmaceuticals (Basel, Switzerland)</title><addtitle>Pharmaceuticals (Basel)</addtitle><description>PMSA (prostate-specific membrane antigen) is currently the most significant target for diagnosing and treating PCa (prostate cancer). Herein, we reported a series
Ga/
Lu-labeled multimer PSMA tracer conjugating with PEG chain, including [
Ga]Ga-DOTA-(1P-PEG
), [
Ga]Ga-DOTA-(2P-PEG
), [
Ga]Ga-DOTA-(2P-PEG
), and [
Ga]Ga/[
Lu]Lu-DOTA-(2P-PEG
)
, which showed an advantage of a multivalent effect and PEGylation to achieve higher tumor accumulation and faster kidney clearance. To figure out how structural optimizations based on a PSMA multimer and PEGylation influence the probe's tumor-targeting ability, biodistribution, and metabolism, we examined PSMA molecular probes' affinities to PC-3 PIP (PSMA-highly-expressed PC-3 cell line), and conducted pharmacokinetics analysis, biodistribution detection, small animal PET/CT, and SPECT/CT imaging. The results showed that PEG
and PSMA dimer optimizations enhanced the probes' tumor-targeting ability in PC-3 PIP tumor-bearing mice models. Compared with the PSMA monomer, the PEGylated PSMA dimer reduced the elimination half-life in the blood and increased uptake in the tumor, and the biodistribution results were consistent with PET/CT imaging results. [
Ga]Ga-DOTA-(2P-PEG
)
exhibited higher tumor-to-organ ratios. When labeled by lutetium-177, relatively high accumulation of DOTA-(2P-PEG
)
was still detected in PC-3 PIP tumor-bearing mice models after 48 h, indicating its prolonged tumor retention time. Given the superiority in imaging, simple synthetic processes, and structural stability, DOTA-(2P-PEG
)
is expected to be a promising tumor-targeting diagnostic molecular probe in future clinical practice.</description><issn>1424-8247</issn><issn>1424-8247</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNqFjs1qAjEURoNYqv15hXJfYNA4acdtEbVCBWG6lzuZ2zE1mQw3iTBbn7wVLHTX1XfgO4szEGOpZiqbz1Qx_MMjcRfC13T6XEglb8UoL6SUuSrG4rxx2JC3vjEa7aSMnHRMjBbKmOoemBrk2rQNxAPBxnXsT1TD7oDsUPujaSkaHaDq4WUOa8zesSJ7MZbr3mK8ULl9hW2y0ThiMC3s2If4c8ECW038IG4-0QZ6vO69eFotPxZvWZcqR_W-Y-OQ-_1vdP6v8A1Ehk_H</recordid><startdate>20230414</startdate><enddate>20230414</enddate><creator>Zhang, Huihui</creator><creator>Rao, Maohua</creator><creator>Zhao, Huayi</creator><creator>Ren, Jianli</creator><creator>Hao, Lan</creator><creator>Zhong, Meng</creator><creator>Chen, Yue</creator><creator>Yang, Xia</creator><creator>Feng, Yue</creator><creator>Yuan, Gengbiao</creator><scope>NPM</scope><orcidid>https://orcid.org/0000-0002-5622-0016</orcidid><orcidid>https://orcid.org/0000-0003-4088-7649</orcidid></search><sort><creationdate>20230414</creationdate><title>Imageological/Structural Study regarding the Improved Pharmacokinetics by 68 Ga-Labeled PEGylated PSMA Multimer in Prostate Cancer</title><author>Zhang, Huihui ; Rao, Maohua ; Zhao, Huayi ; Ren, Jianli ; Hao, Lan ; Zhong, Meng ; Chen, Yue ; Yang, Xia ; Feng, Yue ; Yuan, Gengbiao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_371113473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Huihui</creatorcontrib><creatorcontrib>Rao, Maohua</creatorcontrib><creatorcontrib>Zhao, Huayi</creatorcontrib><creatorcontrib>Ren, Jianli</creatorcontrib><creatorcontrib>Hao, Lan</creatorcontrib><creatorcontrib>Zhong, Meng</creatorcontrib><creatorcontrib>Chen, Yue</creatorcontrib><creatorcontrib>Yang, Xia</creatorcontrib><creatorcontrib>Feng, Yue</creatorcontrib><creatorcontrib>Yuan, Gengbiao</creatorcontrib><collection>PubMed</collection><jtitle>Pharmaceuticals (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Huihui</au><au>Rao, Maohua</au><au>Zhao, Huayi</au><au>Ren, Jianli</au><au>Hao, Lan</au><au>Zhong, Meng</au><au>Chen, Yue</au><au>Yang, Xia</au><au>Feng, Yue</au><au>Yuan, Gengbiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Imageological/Structural Study regarding the Improved Pharmacokinetics by 68 Ga-Labeled PEGylated PSMA Multimer in Prostate Cancer</atitle><jtitle>Pharmaceuticals (Basel, Switzerland)</jtitle><addtitle>Pharmaceuticals (Basel)</addtitle><date>2023-04-14</date><risdate>2023</risdate><volume>16</volume><issue>4</issue><issn>1424-8247</issn><eissn>1424-8247</eissn><abstract>PMSA (prostate-specific membrane antigen) is currently the most significant target for diagnosing and treating PCa (prostate cancer). Herein, we reported a series
Ga/
Lu-labeled multimer PSMA tracer conjugating with PEG chain, including [
Ga]Ga-DOTA-(1P-PEG
), [
Ga]Ga-DOTA-(2P-PEG
), [
Ga]Ga-DOTA-(2P-PEG
), and [
Ga]Ga/[
Lu]Lu-DOTA-(2P-PEG
)
, which showed an advantage of a multivalent effect and PEGylation to achieve higher tumor accumulation and faster kidney clearance. To figure out how structural optimizations based on a PSMA multimer and PEGylation influence the probe's tumor-targeting ability, biodistribution, and metabolism, we examined PSMA molecular probes' affinities to PC-3 PIP (PSMA-highly-expressed PC-3 cell line), and conducted pharmacokinetics analysis, biodistribution detection, small animal PET/CT, and SPECT/CT imaging. The results showed that PEG
and PSMA dimer optimizations enhanced the probes' tumor-targeting ability in PC-3 PIP tumor-bearing mice models. Compared with the PSMA monomer, the PEGylated PSMA dimer reduced the elimination half-life in the blood and increased uptake in the tumor, and the biodistribution results were consistent with PET/CT imaging results. [
Ga]Ga-DOTA-(2P-PEG
)
exhibited higher tumor-to-organ ratios. When labeled by lutetium-177, relatively high accumulation of DOTA-(2P-PEG
)
was still detected in PC-3 PIP tumor-bearing mice models after 48 h, indicating its prolonged tumor retention time. Given the superiority in imaging, simple synthetic processes, and structural stability, DOTA-(2P-PEG
)
is expected to be a promising tumor-targeting diagnostic molecular probe in future clinical practice.</abstract><cop>Switzerland</cop><pmid>37111347</pmid><orcidid>https://orcid.org/0000-0002-5622-0016</orcidid><orcidid>https://orcid.org/0000-0003-4088-7649</orcidid></addata></record> |
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source | DOAJ Directory of Open Access Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
title | Imageological/Structural Study regarding the Improved Pharmacokinetics by 68 Ga-Labeled PEGylated PSMA Multimer in Prostate Cancer |
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