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.
authors: Jessie R
authors: JR
authors: Nedrow
authors: Alexander G
authors: AG
authors: White
authors: Jalpa
authors: J
authors: Modi
authors: Kim
authors: K
authors: Nguyen
authors: Albert J
authors: AJ
authors: Chang
authors: Carolyn J
authors: CJ
authors: Anderson
mesh_terms: D000085:Acetates / Q000378:metabolism; D000818:Animals; D002614:Chelating Agents / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging*; D003301:Copper Radioisotopes / Q000493:pharmacokinetics*; D005260:Female; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics*; D045325:HCT116 Cells; D006571:Heterocyclic Compounds / Q000378:metabolism; D006573:Heterocyclic Compounds, 1-Ring / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010456:Peptides, Cyclic / Q000378:metabolism*; D049268:Positron-Emission Tomography; D013004:Somatostatin / Q000819:agonists*; D014055:Tomography, Emission-Computed
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D002614:Chelating Agents; D003301:Copper Radioisotopes; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D010456:Peptides, Cyclic; C470036:octreotate, Tyr(3)-; D013004:Somatostatin; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid