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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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111In-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-Phe(4-NO2)-cyclo(D-Cys-Tyr-D-Trp-Lys-Thr-Cys)-D-Tyr-NH2

, PhD
National for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: October 15, 2009.

Chemical name:111In-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-Phe(4-NO2)-cyclo(D-Cys-Tyr-D-Trp-Lys-Thr-Cys)-D-Tyr-NH2
Abbreviated name:111In-DOTA-sst2-ANT
Agent category:Peptide
Target:Somatostatin receptor (sst2)
Target category:Receptor
Method of detection:Single-photon emission computed tomography (SPECT), gamma planar imaging
Source of signal:111In
  • Checkbox In vitro
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about somatostatin.



Somatostatin (SST) is an inhibitor of the release of somatotropin, glucagon, insulin, gastrointestinal hormones, and other secretory proteins (1). SST is also known as somatotropin release-inhibiting factor (SRIF). SST is a cyclic polypeptide with two biologically active isoforms, SRIF-14 and SRIF-28, of 14 and 28 amino acids, respectively. SRIF has a short plasma half-life of <3 min (2). SST receptors (SSTRs) (G-protein–coupled) have been found on a variety of neuroendocrine tumors and cells of the immune system, and five individual subtypes (sst1–sst5) have been identified and subsequently cloned from animal and human tissues (3, 4). SST also inhibits cell proliferation and promotes apoptosis through binding to specific cell-surface SSTRs (5).

111In-Labeled diethylenetriaminepentaacetic acid-octreotide (111In-DTPA-OCT) is an SST analog that, over the last decade, has remained the most widely used radiopharmaceutical for the scintigraphic detection and staging of primary and metastatic neuroendocrine tumors bearing SSTRs with single-photon emission computed tomography (SPECT) (6). It has also shown promising results in peptide-receptor radionuclide therapy (7). Octreotide (OCT) is a cyclic peptide with eight amino acids. 111In-DTPA-OCT binds with high affinity to SSTR subtypes 2 and 5 (sst2 and sst5) and to sst3 to a lesser degree, but it does not bind to sst1 and sst4 (8). Currently used targeting SSTR peptides mainly are sst2 agonists. Therefore, there is a need for sst2 antagonist radioligands (9). Ginj et al. (10) have developed a series of SST antagonist ligands. One of them, Phe(4-NO2)-cyclo(D-Cys-Tyr-D-Trp-Lys-Thr-Cys)-D-Tyr-NH2 (sst2-ANT), was found to be a selective sst2 antagonist. For evaluation as a SPECT imaging agent for sst2, 64Cu has been attached to sst2-ANT via tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) to form 111In-DOTA-sst2-ANT.



DOTA-sst2-ANT was synthesized via standard solid-phase peptide synthesis (10). DOTA was incorporated at the N-terminus of the peptide. DOTA-sst2-ANT was purified with high-performance liquid chromatography. Radiolabeling of DOTA-sst2-ANT with 111In was not reported. 111In-DOTA-sst2-ANT had a specific activity of ~20 GBq/µmol (0.54 Ci/µmol).

In Vitro Studies: Testing in Cells and Tissues


Ginj et al. (10) reported that In-DOTA-sst2-ANT had 50% inhibition concentration (IC50) values of >1,000, 9.4 ± 0.4, >1,000, 380 ± 57, and >1,000 nM for human sst1, sst2, sst3, sst4, and sst5 receptors in competition with 125I-SRIF-28, respectively. Wadas et al. (11) determined that 64Cu-CB-TE2A-sst2-ANT showed a Kd (affinity constant) value of 26.0 ± 2.4 nM and a Bmax (receptor density) value of 23 pmol/mg protein in AR42J (sst2-positive) tumor cell homogenates.

Animal Studies



Ginj et al. (10) performed ex vivo biodistribution studies with 111In-DOTA-sst2-ANT in nude mice (n = 3/group) bearing xenografts of HEK-sst2 cells at 0.5, 4, and 24 h after injection. The accumulation of radioactivity in the sst2 tumors was 22.33% injected dose per gram (% ID/g) at 0.5 h, 29.12% ID/g at 4 h, and 22.84% ID/g at 24 h after injection. The pituitary was the organ that had the highest accumulation (20.33% ID/g) at 4 h after injection, followed by the kidney (10.50% ID/g), bone (1.29% ID/g), pancreas (0.71% ID/g) stomach (0.61% ID/g), and adrenal (0.49% ID/g). Accumulation of radioactivity in the other tissues was low. The concentration in the blood was 0.13% ID/g at 4 h after injection, with a tumor/blood ratio of 208 and a tumor/muscle ratio of 265 at 4 h after injection. Co-injection with DOTA-sst2-ANT reduced the accumulation of radioactivity by 88% in the tumors, 50% in the adrenal and bone, 66% in the stomach, 88% in the pancreas, and 85% in the pituitary at 4 h after injection. Little or no inhibition was observed in the other tissues.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.

NIH Support

R24 CA83060, F32 CA115148, R01 CA064475, R01 EB 1430, R24 CA86307


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Ginj M., Zhang H., Waser B., Cescato R., Wild D., Wang X., Erchegyi J., Rivier J., Macke H.R., Reubi J.C. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proc Natl Acad Sci U S A. 2006;103(44):16436–41. [PMC free article: PMC1618814] [PubMed: 17056720]
Wadas T.J., Eiblmaier M., Zheleznyak A., Sherman C.D., Ferdani R., Liang K., Achilefu S., Anderson C.J. Preparation and biological evaluation of 64Cu-CB-TE2A-sst2-ANT, a somatostatin antagonist for PET imaging of somatostatin receptor-positive tumors. J Nucl Med. 2008;49(11):1819–27. [PMC free article: PMC2794832] [PubMed: 18927338]


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