Positron emission tomographic imaging of copper 64- and gallium 68-labeled chelator conjugates of the somatostatin agonist tyr3-octreotate

Jessie Nedrow, Alexander G. White, Jalpa Modi, Kim Nguyen, Albert J. Chang, Carolyn J. Anderson

Research output: Contribution to journalArticle

Abstract

The bifunctional chelator and radiometal have been shown to have a direct effect on the pharmacokinetics of somatostatin receptor (SSTR)-targeted imaging agents. We evaluated three Y3-TATE analogues conjugated to NOTA-based chelators for radiolabeling with 64Cu and 68Ga for small-animal positron emission tomographic/computed tomographic (PET/CT) imaging. Two commercially available NOTA analogues, p-SCN-Bn-NOTA and NODAGA, were evaluated. The p-SCN-Bn-NOTA analogues were conjugated to Y3-TATE through β-Ala and PEG8 linkages. The NODAGA chelator was directly conjugated to Y3-TATE. The analogues labeled with 64Cu or 68Ga were analyzed in vitro for binding affinity and internalization and in vivo by PET/CT imaging, biodistribution, and Cerenkov imaging (68Ga analogues). We evaluated the effects of the radiometals, chelators, and linkers on the performance of the SSTR subtype 2--targeted imaging agents and also compared them to a previously reported agent, 64Cu-CB-TE2A-Y3-TATE. We found that the method of conjugation, particularly the length of the linkage between the chelator and the peptide, significantly impacted tumor and nontarget tissue uptake and clearance. Among the 64Cu- and 68Ga-labeled NOTA analogues, NODAGA-Y3-TATE had the most optimal in vivo behavior and was comparable to 64Cu-CB-TE2A-Y3-TATE. An advantage of NODAGA-Y3-TATE is that it allows labeling with 64Cu and 68Ga, providing a versatile PET probe for imaging SSTr subtype 2-positive tumors.

Original languageEnglish (US)
JournalMolecular Imaging
Volume13
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Gallium
Positrons
Chelating Agents
Somatostatin
gallium
Copper
positrons
Electrons
analogs
Imaging techniques
copper
linkages
Tumors
tumors
Somatostatin Receptors
Pharmacokinetics
clearances
Neoplasms
conjugation
Labeling

ASJC Scopus subject areas

  • Biotechnology
  • Medicine(all)
  • Biomedical Engineering
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

Cite this

Positron emission tomographic imaging of copper 64- and gallium 68-labeled chelator conjugates of the somatostatin agonist tyr3-octreotate. / Nedrow, Jessie; White, Alexander G.; Modi, Jalpa; Nguyen, Kim; Chang, Albert J.; Anderson, Carolyn J.

In: Molecular Imaging, Vol. 13, 2014.

Research output: Contribution to journalArticle

Nedrow, Jessie ; White, Alexander G. ; Modi, Jalpa ; Nguyen, Kim ; Chang, Albert J. ; Anderson, Carolyn J. / Positron emission tomographic imaging of copper 64- and gallium 68-labeled chelator conjugates of the somatostatin agonist tyr3-octreotate. In: Molecular Imaging. 2014 ; Vol. 13.
@article{61f6a24d3d424e7b897809cbe914b39b,
title = "Positron emission tomographic imaging of copper 64- and gallium 68-labeled chelator conjugates of the somatostatin agonist tyr3-octreotate",
abstract = "The bifunctional chelator and radiometal have been shown to have a direct effect on the pharmacokinetics of somatostatin receptor (SSTR)-targeted imaging agents. We evaluated three Y3-TATE analogues conjugated to NOTA-based chelators for radiolabeling with 64Cu and 68Ga for small-animal positron emission tomographic/computed tomographic (PET/CT) imaging. Two commercially available NOTA analogues, p-SCN-Bn-NOTA and NODAGA, were evaluated. The p-SCN-Bn-NOTA analogues were conjugated to Y3-TATE through β-Ala and PEG8 linkages. The NODAGA chelator was directly conjugated to Y3-TATE. The analogues labeled with 64Cu or 68Ga were analyzed in vitro for binding affinity and internalization and in vivo by PET/CT imaging, biodistribution, and Cerenkov imaging (68Ga analogues). We evaluated the effects of the radiometals, chelators, and linkers on the performance of the SSTR subtype 2--targeted imaging agents and also compared them to a previously reported agent, 64Cu-CB-TE2A-Y3-TATE. We found that the method of conjugation, particularly the length of the linkage between the chelator and the peptide, significantly impacted tumor and nontarget tissue uptake and clearance. Among the 64Cu- and 68Ga-labeled NOTA analogues, NODAGA-Y3-TATE had the most optimal in vivo behavior and was comparable to 64Cu-CB-TE2A-Y3-TATE. An advantage of NODAGA-Y3-TATE is that it allows labeling with 64Cu and 68Ga, providing a versatile PET probe for imaging SSTr subtype 2-positive tumors.",
author = "Jessie Nedrow and White, {Alexander G.} and Jalpa Modi and Kim Nguyen and Chang, {Albert J.} and Anderson, {Carolyn J.}",
year = "2014",
doi = "10.2310/7290.2014.00020",
language = "English (US)",
volume = "13",
journal = "Molecular Imaging",
issn = "1535-3508",
publisher = "Decker Publishing",

}

TY - JOUR

T1 - Positron emission tomographic imaging of copper 64- and gallium 68-labeled chelator conjugates of the somatostatin agonist tyr3-octreotate

AU - Nedrow, Jessie

AU - White, Alexander G.

AU - Modi, Jalpa

AU - Nguyen, Kim

AU - Chang, Albert J.

AU - Anderson, Carolyn J.

PY - 2014

Y1 - 2014

N2 - The bifunctional chelator and radiometal have been shown to have a direct effect on the pharmacokinetics of somatostatin receptor (SSTR)-targeted imaging agents. We evaluated three Y3-TATE analogues conjugated to NOTA-based chelators for radiolabeling with 64Cu and 68Ga for small-animal positron emission tomographic/computed tomographic (PET/CT) imaging. Two commercially available NOTA analogues, p-SCN-Bn-NOTA and NODAGA, were evaluated. The p-SCN-Bn-NOTA analogues were conjugated to Y3-TATE through β-Ala and PEG8 linkages. The NODAGA chelator was directly conjugated to Y3-TATE. The analogues labeled with 64Cu or 68Ga were analyzed in vitro for binding affinity and internalization and in vivo by PET/CT imaging, biodistribution, and Cerenkov imaging (68Ga analogues). We evaluated the effects of the radiometals, chelators, and linkers on the performance of the SSTR subtype 2--targeted imaging agents and also compared them to a previously reported agent, 64Cu-CB-TE2A-Y3-TATE. We found that the method of conjugation, particularly the length of the linkage between the chelator and the peptide, significantly impacted tumor and nontarget tissue uptake and clearance. Among the 64Cu- and 68Ga-labeled NOTA analogues, NODAGA-Y3-TATE had the most optimal in vivo behavior and was comparable to 64Cu-CB-TE2A-Y3-TATE. An advantage of NODAGA-Y3-TATE is that it allows labeling with 64Cu and 68Ga, providing a versatile PET probe for imaging SSTr subtype 2-positive tumors.

AB - The bifunctional chelator and radiometal have been shown to have a direct effect on the pharmacokinetics of somatostatin receptor (SSTR)-targeted imaging agents. We evaluated three Y3-TATE analogues conjugated to NOTA-based chelators for radiolabeling with 64Cu and 68Ga for small-animal positron emission tomographic/computed tomographic (PET/CT) imaging. Two commercially available NOTA analogues, p-SCN-Bn-NOTA and NODAGA, were evaluated. The p-SCN-Bn-NOTA analogues were conjugated to Y3-TATE through β-Ala and PEG8 linkages. The NODAGA chelator was directly conjugated to Y3-TATE. The analogues labeled with 64Cu or 68Ga were analyzed in vitro for binding affinity and internalization and in vivo by PET/CT imaging, biodistribution, and Cerenkov imaging (68Ga analogues). We evaluated the effects of the radiometals, chelators, and linkers on the performance of the SSTR subtype 2--targeted imaging agents and also compared them to a previously reported agent, 64Cu-CB-TE2A-Y3-TATE. We found that the method of conjugation, particularly the length of the linkage between the chelator and the peptide, significantly impacted tumor and nontarget tissue uptake and clearance. Among the 64Cu- and 68Ga-labeled NOTA analogues, NODAGA-Y3-TATE had the most optimal in vivo behavior and was comparable to 64Cu-CB-TE2A-Y3-TATE. An advantage of NODAGA-Y3-TATE is that it allows labeling with 64Cu and 68Ga, providing a versatile PET probe for imaging SSTr subtype 2-positive tumors.

UR - http://www.scopus.com/inward/record.url?scp=85003048277&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85003048277&partnerID=8YFLogxK

U2 - 10.2310/7290.2014.00020

DO - 10.2310/7290.2014.00020

M3 - Article

C2 - 25060207

AN - SCOPUS:84907508890

VL - 13

JO - Molecular Imaging

JF - Molecular Imaging

SN - 1535-3508

ER -