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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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111In-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-MEDI-522

, PhD
National Center for Biotechnology Information, NLM, NIH
Corresponding author.

Created: ; Last Update: June 30, 2011.

Chemical name:111In-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-MEDI-522
Abbreviated name:111In-DOTA-MEDI-522
Synonym:111In-DOTA-Abegrin, 111In-DOTA-Vitaxin
Agent category:Antibody
Target:Integrin αvβ3
Target category:Receptor
Method of detection:Single-photon emission computed tomography (SPECT), gamma planar imaging
Source of signal:111In
  • Checkbox In vitro
  • Checkbox Rodents
Structure is not available in PubChem.



Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell–cell and cell–matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. The αvβ3 integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of the αvβ3 integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. Antagonists of αvβ3 are being studied as antitumor and antiangiogenic agents, and the agonists of αvβ3 are being studied as angiogenic agents for coronary angiogenesis (6, 8, 9). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including αvβ3. Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (10).

Most cyclic RGD peptides are composed of five amino acids. Haubner et al. (11) reported that various cyclic RGD peptides exhibit selective inhibition of binding to αvβ3 (inhibition concentration (IC50), 7–40 nM) but not to integrins αvβ5 (IC50, 600–4,000 nM) or αIIbβ3 (IC50, 700–5,000 nM). Various radiolabeled cyclic RGD peptides have been found to have high accumulation in tumors in nude mice (12). In addition to RGD peptides, a humanized anti-human integrin αvβ3 monoclonal antibody (MEDI-522) was identified to be unique in that it recognizes either the human αv or β3 subunit. MEDI-522 cross-reacts with integrin αvβ3 from rabbits, chickens, and hamsters but not with integrin αvβ3 from mice or rats (13). MEDI-522 is being evaluated as an antiangiogenic agent for cancer therapy (14-16). Cai et al. (17) reported the development of 64Cu-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-MEDI-522 (64Cu-DOTA-MEDI-522) for positron emission tomography imaging of αvβ3 receptors in nude mice bearing tumors. Liu et al. (18) reported the evaluation of 111In-DOTA-MEDI-522 for single-photon emission computed tomography (SPECT) imaging αvβ3 receptors in nude mice bearing tumors.



DOTA was incubated with EDC and SNHS for 30 min at pH 5.5 with a molar ratio of 10:5:4 (18). The product, DOTA-N-hydroxysulfosuccinimidyl (DOTA-OSSu), was added to MEDI-522 in a molar ratio of 200:1 (DOTA-OSSu/MEDI-522). The reaction mixture was adjusted to pH 8.5 and incubated for ~18 h at 4°C. DOTA-MEDI-522 was purified with column chromatography. DOTA-MEDI-522 (0.33 nmol) was incubated with 74 MBq (2 mCi) 111InCl3 in sodium acetate buffer (pH 5.5) for 1 h at 39°C. 111In-DOTA-MEDI-522 was purified with column chromatography. There were ~10 DOTA moieties per 111In-DOTA-MEDI-522. The immunoreactivity was determined to be >90% with integrin αvβ3-positive U87MG human glioblastoma cells. The radiolabeling yield and specific activity of 111In-DOTA-MEDI-522 were not reported.

In Vitro Studies: Testing in Cells and Tissues


Liu et al. (18) performed saturation binding studies of 125I-MEDI-522 on U87MG cells. 125I-MEDI-522 showed a Kd value (affinity constant) of 0.35 ± 0.06 nM and a Bmax value (receptor density) of 2.5 × 105 sites per cell. MEDI-522 and DOTA-MEDI-522 exhibited an inhibition curve similar to that of 125I-MEDI-522 binding to U87MG cells. Little binding of 125I-MEDI-522 was observed in HT-29 human colon tumor cells.

Animal Studies



Liu et al. (18) performed ex vivo biodistribution studies of 0.74 MBq (0.2 mCi) 111In-DOTA-MEDI-522 in nude mice (n = 4/group) bearing human U87MG tumors at 4, 24, 72, 120, and 168 h after injection. Tumor accumulation was 6.19 ± 1.16% injected dose/gram (ID/g), 14.12 ± 0.44% ID/g, 14.85 ± 4.73% ID/g, 11.47 ± 3.51% ID/g, and 11.40 ± 0.07% ID/g at 4, 24, 72, 120, and 168 h after injection, respectively. Radioactivity levels in the blood were 31.3% ID/g and 1.17% ID/g at 4 h and 168 h, respectively. Accumulation in the liver and spleen was 20% ID/g and 16% ID/g at 24 h after injection, respectively. The other normal organs showed less accumulation than the tumor. Co-injection of excess MEDI-522 inhibited tumor accumulation by ~50% at 24 h after injection (P < 0.01). Little inhibition was observed in other normal organs (heart, liver, kidney, and spleen).

SPECT imaging scans were performed in nude mice (n = 3) bearing both U87MG human glioblastoma tumors (high integrin αvβ3 expression) and HT-29 human colon adenocarcinoma tumors (low integrin αvβ3 expression) after injection of 11.1 MBq (0.3 mCi) 111In-DOTA-MEDI-522. Radioactivity accumulation was mainly visualized in the heart and abdomen at 2 h after injection. At 24 h, both tumors were gradually visualized. Accumulation of radioactivity was higher in the U87MG tumors than in the HT-29 tumors at 120 h after injection as the radioactivity was cleared from the normal organs. Immunofluorescence staining of tumor sections confirmed binding of MEDI-522 to U87MG tumor cells and not to HT-29 tumor cells. There was no co-localization of MEDI-522 to tumor vasculature in mice with U87MG tumors because MEDI-522 does not cross-react with mouse integrin αvβ3. Anti-mouse β3 antibody binding was observed only in mouse tumor vasculature.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.


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