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Preparation and Biological Evaluation of Cu-64-CB-TE2A-sst(2)-ANT, a Somatostatin Antagonist for PET Imaging of Somatostatin Receptor-Positive Tumors
Journal article   Open access   Peer reviewed

Preparation and Biological Evaluation of Cu-64-CB-TE2A-sst(2)-ANT, a Somatostatin Antagonist for PET Imaging of Somatostatin Receptor-Positive Tumors

Thaddeus J. Wadas, Martin Eiblmaier, Alexander Zheleznyak, Christopher D. Sherman, Riccardo Ferdani, Kexian Liang, Samuel Achilefu and Carolyn J. Anderson
The Journal of nuclear medicine (1978), Vol.49(11), pp.1819-1827
11/01/2008
DOI: 10.2967/jnumed.108.054502
PMCID: PMC2794832
PMID: 18927338
url
https://doi.org/10.2967/jnumed.108.054502View
Published (Version of record) Open Access

Abstract

Recently, the somatostatin receptor subtype 2 (SSTR2) selective antagonist sst(2)-ANT was determined to have a high affinity for SSTR2. Additionally, In-111-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-sst(2)-ANT showed high uptake in an SSTR2-transfected, tumor-bearing mouse model and suggested that radiolabeled SSTR2 antagonists may be superior to agonists for imaging SSTR2-positive tumors. This report describes the synthesis and evaluation of Cu-64-CB-4,11-bis(carboxymethyl)1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-sst(2)-ANT (Cu-64-CBTE2A-sst(2)-ANT) as a PET radiopharmaceutical for the in vivo imaging of SSTR2-positive tumors. Methods: Receptor-binding studies were performed to determine the dissociation constant of the radio pharmaceutical Cu-64-CB-TE2A-sst(2)-ANT using AR42J rat pancreatic tumor cell membranes. The internalization of Cu-64-CB-TE2A-sst(2)-ANT was compared with that of the Cu-64-labeled agonist Cu-64-CB-TE2A-tyrosine(3)-octreotate (Cu-64-CB-TE2A-Y3-TATE) in AR42J cells. Both radiopharmaceuticals were also compared in vivo through biodistribution studies using healthy rats bearing AR42J tumors, and small-animal PET/CT of Cu-64-CB-TE2A-sst(2)-ANT was performed. Results: The dissociation constant value for the radiopharmaceutical was determined to be 26 +/- 2.4 nM, and the maximum number of binding sites was 23,000 fmol/mg. Cu-64-CB-TE2A-sst(2)-ANT showed significantly less internalization than did 64Cu-CB-TE2A-Y3-TATE at time points from 15 min to 4 h. Biodistribution studies revealed that the clearance of Cu-64-CBTE2A-sst(2)-ANT from the blood was rapid, whereas the clearance of Cu-64-CB-TE2A-sst(2)-ANT from the liver and kidneys was more modest at all time points. Tumor-to-blood and tumor-to-muscle ratios were determined to be better for Cu-64-CB-TE2A-sst(2)-ANT than those for Cu-64-CB-TE2A-Y3-TATE at the later time points, although liver and kidney uptake was significantly higher. Small-animal imaging using Cu-64-CB-TE2A-sst(2)-ANT revealed excellent tumor-to-background contrast at 4 h after injection, and standardized uptake values remained high even after 24 h. Conclusion: The PET radiopharmaceutical Cu-64-CB-TE2A-sst(2)-ANT is an attractive agent, worthy of future study as a PET radiopharmaceutical for the imaging of somatostatin receptor-positive tumors.
 Life Sciences & Biomedicine Radiology, Nuclear Medicine & Medical Imaging Science & Technology

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