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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-Diethylenetriaminepentaacetic acid-2C5 monoclonal antibody

111In-DTPA-2C5
, PhD
National for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: June 6, 2009.

Chemical name:111In-Diethylenetriaminepentaacetic acid-2C5
Abbreviated name:111In-DTPA-2C5
Synonym:
Agent category:Antibody
Target:Nucleosome-specific antinuclear autoantibodies (ANA)
Target category:Antigen
Method of detection:Single-photon emission computed tomography, gamma planar imaging
Source of signal:111In
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
No structure is available in PubChem.

Background

[PubMed]

Natural autoantibodies are produced when the immune system recognizes one or more of the body's normal constituents as foreign. These autoantibodies attack the body's own cells, tissues, or organs, leading to systemic autoimmune diseases. Nucleosome-specific anti-nuclear autoantibodies (ANAs) have been found to exhibit anti-tumor activity (1). The nucleosomes targeted by these antibodies are released from the dying tumor cells and bind to the adjacent healthy tumor cells, leading to the formation of ANAs specific to the nucleosomes (2). The nucleosome-specific ANA monoclonal antibody (mAb) 2C5 was found to have anti-tumor activity against a variety of experimental tumor models but showed no recognition of normal cells (1). There was an increased survival rate in cancer patients with elevated levels of serum ANAs (3, 4). 111In-Diethylenetriaminepentaacetic acid-2C5 (111In-DTPA-2C5) has been studied for imaging ANA expression in nude mice bearing diverse human cancer xenografts (5, 6).

Synthesis

[PubMed]

Samokhin et al. (7) reported the radiolabeling of the mAb 2C5. DTPA-anhydride (0.5 mM) was added to a solution of the mAb 2C5 (~7 nmol) and dextran sulphate (MW, 10 kDa). The mixture was incubated for 1 h at room temperature. Excess DTPA was removed with dialysis. DTPA-2C5 was mixed with 1.11 MBq (0.03 mCi) 111InCl3 in citrate buffer (pH 3). The mixture was incubated for 60 min at room temperature. Excess 111In was removed from 111In-DTPA-2C5 with overnight dialysis. The 111In-labeling efficiency was 80% with a specific activity of 0.49 MBq/nmol (0.013 mCi/nmol). The radiochemical purity and the number of DTPA molecules per antibody were not reported.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Chakilam et al. (5) showed that the binding affinity (Kd) of 2C5 mAb for nucleosomes was 0.24 ± 0.06 nM. Flow cytometry analyses confirmed 2C5 mAb binding to eight broad variety human tumor cell lines (COLO-205, PC-3, C32TG, NCI-H82, MCF7, H9, H69 AR, and BT-20). DTPA-2C5 and 2C5 mAb exhibited similar immunoreactivity for immobilized nucleosomes.

Animal Studies

Rodents

[PubMed]

Chakilam et al. (5) performed biodistribution studies with 111In-DTPA-2C5 in mice bearing five broad variety human tumor xenografts (COLO-205, PC-3, C32TG, NCI-H82, and BT-20). The tumor/muscle ratios were 2.7–13.4 at 2 d after injection. Radioactivity levels in normal tissues/organs were not reported. Single-photon emission computed tomography scintigraphic imaging showed radioactivity as early as 6 h after injection and clearly visualized the radioactivity by 24 h, with high radioactivity in the abdomen area. Elbayoumi et al. (6) repeated the tumor accumulation study of 111In-DTPA-2C5 with two human tumor cell lines (COLO-205 and PC-3), which exhibited tumor/muscle ratios of 2.7 and 6.3 at 48 h, respectively. 111In-DTPA-2C5 liposomes exhibited tumor/muscle ratios of 6.0 for COLO-205 and 16.3 for PC-3 at 48 h, which were higher than the ratios obtained with 111In-DTPA-2C5 and 111In-labeled liposomes. High uptake of 111In-DTPA-2C5 liposomes was observed in the liver, spleen, and kidneys at just 3 h. No blocking experiments were 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

R01 EB01961, R01 EB02995, 2R01 HL55519

References

1.
Iakoubov L.Z., Torchilin V.P. A novel class of antitumor antibodies: nucleosome-restricted antinuclear autoantibodies (ANA) from healthy aged nonautoimmune mice. Oncol Res. 1997;9(8):439–46. [PubMed: 9436197]
2.
Iakoubov L.Z., Torchilin V.P. Nucleosome-releasing treatment makes surviving tumor cells better targets for nucleosome-specific anticancer antibodies. Cancer Detect Prev. 1998;22(5):470–5. [PubMed: 9727629]
3.
Blaes F., Klotz M., Huwer H., Straub U., Kalweit G., Schimrigk K., Schafers H.J. Antineural and antinuclear autoantibodies are of prognostic relevance in non-small cell lung cancer. Ann Thorac Surg. 2000;69(1):254–8. [PubMed: 10654525]
4.
Syrigos K.N., Charalambopoulos A., Pliarchopoulou K., Varsamidakis N., Machairas A., Mandrekas D. The prognostic significance of autoantibodies against dsDNA in patients with colorectal adenocarcinoma. Anticancer Res. 2000;20(6B):4351–3. [PubMed: 11205270]
5.
Chakilam A.R., Pabba S., Mongayt D., Iakoubov L.Z., Torchilin V.P. A single monoclonal antinuclear autoantibody with nucleosome-restricted specificity inhibits growth of diverse human tumors in nude mice. Cancer Therapy. 2004;2:353–364.
6.
Elbayoumi T.A., Pabba S., Roby A., Torchilin V.P. Antinucleosome antibody-modified liposomes and lipid-core micelles for tumor-targeted delivery of therapeutic and diagnostic agents. J Liposome Res. 2007;17(1):1–14. [PubMed: 17454399]
7.
Samokhin G.P., Mongayt D.A., Iakoubov L.Z., Levchenko T.S., Torchilin V.P. Negatively charged polymers protect antinuclear antibody against inactivation by acylating agents. Anal Biochem. 2001;292(2):245–9. [PubMed: 11355857]

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