Preparation and Biological Evaluation of 64Cu-CB-TE2A-sst2-ANT, a Somatostatin Antagonist for PET Imaging of Somatostatin Receptor–Positive Tumors
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UNLABELLED: Recently, the somatostatin receptor subtype 2 (SSTR2) selective antagonist sst2-ANT was determined to have a high affinity for SSTR2. Additionally, 111In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-sst2-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 64Cu-CB-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-sst2-ANT (64Cu-CB-TE2A-sst2-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 radiopharmaceutical 64Cu-CB-TE2A-sst2-ANT using AR42J rat pancreatic tumor cell membranes. The internalization of 64Cu-CB-TE2A-sst2-ANT was compared with that of the 64Cu-labeled agonist 64Cu-CB-TE2A-tyrosine3-octreotate (64Cu-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 64Cu-CB-TE2A-sst2-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. 64Cu-CB-TE2A-sst2-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 64Cu-CB-TE2A-sst2-ANT from the blood was rapid, whereas the clearance of 64Cu-CB-TE2A-sst2-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 64Cu-CB-TE2A-sst2-ANT than those for 64Cu-CB-TE2A-Y3-TATE at the later time points, although liver and kidney uptake was significantly higher. Small-animal imaging using 64Cu-CB-TE2A-sst2-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 64Cu-CB-TE2A-sst2-ANT is an attractive agent, worthy of future study as a PET radiopharmaceutical for the imaging of somatostatin receptor-positive tumors.
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BASS labeled with 64Cu via the chelator CB-TE2A showed a compromised tumor uptake compared to the agonist 64Cu-CB-TE2A-octreotate in SSTR2-positive AR42J xenografts.
“Despite this, BASS labeled with 64Cu via the chelator 4, 11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo [6.6.2]hexadecane (CB-TE2A) (64Cu-CB-TE2A-BASS) showed a compromised tumor uptake compared to the agonist 64Cu-CB-TE2A-octreotate in SSTR2-positive AR42J xenografts (129).”
From Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists (2022) · cites this paper as [129]
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References 28 · Cited by 73
- Authors
- Wadas, T. J., Eiblmaier, M., Zheleznyak, A., Sherman, C. D., Ferdani, R., Liang, K., Achilefu, S., & Anderson, C. J.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Anderson, Carolyn J.
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2008-10-16
- Volume
- 49
- Issue
- 11
- Pages
- 1819-1827
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- PMC
- PMC2794832
- OpenAlex
- W2005389389
- Cited by
- 73
- References
- 28
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 7 · 2016: 3 · 2015: 9 · 2014: 5 · 2013: 7 · 2012: 6
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Strong
- National Institutes of Health (R24 CA86307)
- National Cancer Institute (R24CA083060, R24CA086307, 5 R24 CA83060, R01CA064475, F32CA115148, R24-CA86307)
- National Institute of Biomedical Imaging and Bioengineering (R01EB1430, R01EB001430)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- somatostatin receptor 2, copper-64 radiolabeling, PET radiopharmaceuticals, tumor imaging, receptor internalization, tissue distribution, dissociation constant, somatostatin receptor-positive tumors
- MeSH terms
- Amino Acid Sequence, Animals, Male, Neoplasms, Organometallic Compounds, Peptides, Radiochemistry, Tissue Distribution, Receptors, Somatostatin, Radiopharmaceuticals, Cell Line, Tumor, Positron-Emission Tomography, Rats
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