Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer

Ying Chen; Catherine A. Foss; Youngjoo Byun; Sridhar Nimmagadda; Mrudula Pullambhatla; James J. Fox; Mark Castanares; Shawn E. Lupold; John W. Babich; Ronnie C. Mease; Martin G. Pomper

doi:10.1021/jm801055h

Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer

Ying Chen, Catherine A. Foss, Youngjoo Byun, Sridhar Nimmagadda, Mrudula Pullambhatla, James J. Fox, Mark Castanares, Shawn E. Lupold, John W. Babich, Ronnie C. Mease, Martin G. Pomper

School of Medicine

Research output: Contribution to journal › Article › peer-review

149 Scopus citations

Abstract

To extend our development of new imaging agents targeting the prostate-specific membrane antigen (PSMA), we have used the versatile intermediate 2-[3-(5-amino-1-carboxy-pentyl)-ureido]-pentanedioic acid (Lys-C(O)-Glu), which allows ready incorporation of radiohalogens for single photon emission computed tomography (SPECT) and positron emission tomography (PET). We prepared 2-[3-[1-carboxy-5-(4-[¹²⁵I]iodo-benzoylamino)- pentyl]-ureido]-pentanedioic acid ([¹²⁵I]3), 2-[3-[1-carboxy-5-(4- [¹⁸F]fluoro-benzoylamino)-pentyl]-ureido]-pentanedioic acid ([ ¹⁸F]6), and 2-(3-[1-carboxy-5-[(5-[¹²⁵I]iodo-pyridine-3- carbonyl)-amino]-pentyl]-ureido)-pentanedioic acid ([¹²⁵I]8) in 65-80% (nondecay-corrected), 30-35% (decay corrected), and 59-75% (nondecay-corrected) radiochemical yields. Compound [¹²⁵I]3 demonstrated 8.8 ± 4.7% injected dose per gram (%ID/g) within PSMA ⁺ PC-3 PIP tumor at 30 min postinjection, which persisted, with clear delineation of the tumor by SPECT. Similar tumor uptake values at early time points were demonstrated for [¹⁸F]6 (using PET) and [ ¹²⁵I]8. Because of the many radiohalogenated moieties that can be attached via the ε amino group, the intermediate Lys-C(O)-Glu is an attractive template upon which to develop new imaging agents for prostate cancer.

Original language	English (US)
Pages (from-to)	7933-7943
Number of pages	11
Journal	Journal of medicinal chemistry
Volume	51
Issue number	24
DOIs	https://doi.org/10.1021/jm801055h
State	Published - Dec 25 2008

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm801055h

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@article{57c719ea0c9c40f7b8f40791f7f8ddf5,

title = "Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer",

abstract = "To extend our development of new imaging agents targeting the prostate-specific membrane antigen (PSMA), we have used the versatile intermediate 2-[3-(5-amino-1-carboxy-pentyl)-ureido]-pentanedioic acid (Lys-C(O)-Glu), which allows ready incorporation of radiohalogens for single photon emission computed tomography (SPECT) and positron emission tomography (PET). We prepared 2-[3-[1-carboxy-5-(4-[125I]iodo-benzoylamino)- pentyl]-ureido]-pentanedioic acid ([125I]3), 2-[3-[1-carboxy-5-(4- [18F]fluoro-benzoylamino)-pentyl]-ureido]-pentanedioic acid ([ 18F]6), and 2-(3-[1-carboxy-5-[(5-[125I]iodo-pyridine-3- carbonyl)-amino]-pentyl]-ureido)-pentanedioic acid ([125I]8) in 65-80% (nondecay-corrected), 30-35% (decay corrected), and 59-75% (nondecay-corrected) radiochemical yields. Compound [125I]3 demonstrated 8.8 ± 4.7% injected dose per gram (%ID/g) within PSMA + PC-3 PIP tumor at 30 min postinjection, which persisted, with clear delineation of the tumor by SPECT. Similar tumor uptake values at early time points were demonstrated for [18F]6 (using PET) and [ 125I]8. Because of the many radiohalogenated moieties that can be attached via the ε amino group, the intermediate Lys-C(O)-Glu is an attractive template upon which to develop new imaging agents for prostate cancer.",

author = "Ying Chen and Foss, {Catherine A.} and Youngjoo Byun and Sridhar Nimmagadda and Mrudula Pullambhatla and Fox, {James J.} and Mark Castanares and Lupold, {Shawn E.} and Babich, {John W.} and Mease, {Ronnie C.} and Pomper, {Martin G.}",

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language = "English (US)",

volume = "51",

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T1 - Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer

AU - Chen, Ying

AU - Foss, Catherine A.

AU - Byun, Youngjoo

AU - Nimmagadda, Sridhar

AU - Pullambhatla, Mrudula

AU - Fox, James J.

AU - Castanares, Mark

AU - Lupold, Shawn E.

AU - Babich, John W.

AU - Mease, Ronnie C.

AU - Pomper, Martin G.

PY - 2008/12/25

Y1 - 2008/12/25

N2 - To extend our development of new imaging agents targeting the prostate-specific membrane antigen (PSMA), we have used the versatile intermediate 2-[3-(5-amino-1-carboxy-pentyl)-ureido]-pentanedioic acid (Lys-C(O)-Glu), which allows ready incorporation of radiohalogens for single photon emission computed tomography (SPECT) and positron emission tomography (PET). We prepared 2-[3-[1-carboxy-5-(4-[125I]iodo-benzoylamino)- pentyl]-ureido]-pentanedioic acid ([125I]3), 2-[3-[1-carboxy-5-(4- [18F]fluoro-benzoylamino)-pentyl]-ureido]-pentanedioic acid ([ 18F]6), and 2-(3-[1-carboxy-5-[(5-[125I]iodo-pyridine-3- carbonyl)-amino]-pentyl]-ureido)-pentanedioic acid ([125I]8) in 65-80% (nondecay-corrected), 30-35% (decay corrected), and 59-75% (nondecay-corrected) radiochemical yields. Compound [125I]3 demonstrated 8.8 ± 4.7% injected dose per gram (%ID/g) within PSMA + PC-3 PIP tumor at 30 min postinjection, which persisted, with clear delineation of the tumor by SPECT. Similar tumor uptake values at early time points were demonstrated for [18F]6 (using PET) and [ 125I]8. Because of the many radiohalogenated moieties that can be attached via the ε amino group, the intermediate Lys-C(O)-Glu is an attractive template upon which to develop new imaging agents for prostate cancer.

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Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer

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