Positron Emission Tomographic Imaging of Copper 64– and Gallium 68–Labeled Chelator Conjugates of the Somatostatin Agonist Tyr3-Octreotate

• Published in: Molecular imaging Vol. 13; no. 7
• Main Authors: Nedrow, Jessie R., White, Alexander G., Modi, Jalpa, Nguyen, Kim, Chang, Albert J., Anderson, Carolyn J.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 2014
• Subjects: Acetates - metabolism; Animals; Chelating Agents - metabolism; Colorectal Neoplasms - diagnostic imaging; Copper Radioisotopes - pharmacokinetics; Female; Gallium Radioisotopes - pharmacokinetics; HCT116 Cells; Heterocyclic Compounds - metabolism; Heterocyclic Compounds, 1-Ring - metabolism; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Peptides, Cyclic - metabolism; Positron-Emission Tomography; Somatostatin - agonists; Tomography, Emission-Computed
• ISSN: 1535-3508; 1536-0121
• DOI: 10.2310/7290.2014.00020

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 tomograhic (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.