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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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64Cu-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-HB22.7

64Cu-DOTA-HB22.7
, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: May 15, 2009.

Chemical name:64Cu-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-HB22.7
Abbreviated name:64Cu-DOTA-HB22.7
Synonym:
Agent category:Antibody
Target:CD22
Target category:Antigen
Method of detection:Positron emission tomography (PET)
Source of signal:64Cu
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Click on protein and gene for more information about the CD22.

Background

[PubMed]

CD22 is a transmembrane glycoprotein found on B lymphocytes. It functions as an adhesion molecule binding to sialic acid–bearing ligands with an immunoglobulin (Ig) domain and also modulates signal transduction via the B-cell receptor (1). CD22 is expressed on the cell surface of mature B cells and non-Hodgkin’s lymphomas (2). HB22.7, an anti-CD22 monoclonal antibody (mAb), blocks the interaction of the Ig domain of CD22 with its ligands to induce proliferation in primary B cells and apoptosis in neoplastic B cells (3, 4). 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) has been successfully coupled to HB22.7 and labeled with 64Cu to produce a potential molecular imaging agent to target non-Hodgkin’s lymphomas (5). 64Cu is a positron emitter with a physical half-life of 12.7 h and is suitable for positron emission tomography (PET) imaging.

Synthesis

[PubMed]

Martin et al. (5) reported the synthesis of 64Cu-DOTA-HB22.7. The HB22.7 mAb (67 nM) was incubated with 670 nM DOTA-NHS-ester in 0.1 M tetramethyl ammonium phosphate (pH 8.0) for 2.5 h at 37°C. DOTA-HB22.7 was isolated with column filtration. There were 6.3 DOTA molecules per antibody molecule. A mixture of DOTA-HB22.7 and 64Cu in 0.25 M ammonium acetate was incubated at 40°C for 40–60 min. 64Cu-DOTA-HB22.7 was purified with column filtration with a radiochemical yield of 83%. The radiochemical purity was >99% with a specific activity of 56 MBq/nmol (1.5 mCi/nmol) at the time of injection.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Martin et al. (5) performed flow cytometric analysis with DOTA-HB22.7 and HB22.7 using the CD22-expressing human Raji lymphoma cell line with a fluorescent-labeled anti-IgG as the secondary antibody. Binding of DOTA-HB22.7 and HB22.7 to Raji cells exhibited the same mean fluorescent intensity of 110 units, indicating that the immunoreactivity of DOTA-HB22.7 was similar to the parent mAb.

Animal Studies

Rodents

[PubMed]

Martin et al. (5) performed PET imaging studies in nude mice (n = 3/group) bearing Raji tumor xenografts. Each mouse received 7.4 MBq (0.2 mCi) 64Cu-DOTA-HB22.7 by intravenous injection. The radioactivity levels were obtained at 3 h, 24 h, and 48 h after injection, with tumor uptake values in percent injected dose per cc (% ID/cc) of 1.8, 5.5, and 6.8, respectively; tumor retention was high. Intraperitoneal and subcutaneous injections showed similar tumor uptakes at 24 and 48 h. Biodistribution studies at 48 h showed that the tumor (~18% ID/g) and blood (17–24% ID/g) exhibited the highest radioactivity levels for the three routes of injections. The distribution patterns to other nontargeted organs were similar with the exception of the spleen (14% ID/g), which showed the highest uptake with the intraperitoneal route compared with the other two routes (8% ID/g). The liver, kidneys, heart, lungs, and urinary bladder had similar radioactivity levels of ~5% ID/g. No blocking experiment was performed.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

NIH Support

R24 CA86307, R24 CA110804, R33 CA89706

References

1.
Tedder T.F., Tuscano J., Sato S., Kehrl J.H. CD22, a B lymphocyte-specific adhesion molecule that regulates antigen receptor signaling. Annu Rev Immunol. 1997;15:481–504. [PubMed: 9143697]
2.
Haas K.M., Sen S., Sanford I.G., Miller A.S., Poe J.C., Tedder T.F. CD22 ligand binding regulates normal and malignant B lymphocyte survival in vivo. J Immunol. 2006;177(5):3063–73. [PubMed: 16920943]
3.
Tedder T.F., Poe J.C., Haas K.M. CD22: A Multifunctional Receptor That Regulates B Lymphocyte Survival and Signal Transduction. Adv Immunol. 2005;88:1–50. [PubMed: 16227086]
4.
Tuscano J.M., Riva A., Toscano S.N., Tedder T.F., Kehrl J.H. CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade. Blood. 1999;94(4):1382–92. [PubMed: 10438726]
5.
Martin, S.M., R.T. O'Donnell, D.L. Kukis, C.K. Abbey, H. McKnight, J.L. Sutcliffe, and J.M. Tuscano, Imaging and Pharmacokinetics of (64)Cu-DOTA-HB22.7 Administered by Intravenous, Intraperitoneal, or Subcutaneous Injection to Mice Bearing Non-Hodgkin's Lymphoma Xenografts. Mol Imaging Biol, 2008. [PubMed: 18949521]

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