NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

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

Cover of Molecular Imaging and Contrast Agent Database (MICAD)

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

Show details

111In-Anti-CD105 MJ7/18 monoclonal antibody

111In-MJ7/18 MAb
, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD, vog.hin.mln.ibcn@dacim

Created: ; Last Update: December 21, 2007.

Chemical name:111In-Anti-CD-105 MJ7/18 monoclonal antibody
Abbreviated name:111In-MJ7/18 MAb
Synonym:111In-labeled- anti-endoglin MAb, 111In-anti-endoglin MAb, 111In-anti-EDG MAb, 111In-DTPA-MJ7/18 MAb, 111In-anti-TGF-ß binding receptor MAb
Agent Category:Antibody
Target:Endoglin (CD105, EDG)
Target Category:Antibody to antigen binding
Method of detection:Single-photon emission computed tomography (SPECT), Gamma planar imaging
Source of signal:111In
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about CD105

Background

[PubMed]

111In-Anti-CD105 MJ7/18 monoclonal antibody (111In-MJ7/18 MAb), which is formed by the 111In conjugation of an intact rat antimouse MJ7/18 MAb against the antigen endoglin (cluster of differentiation 105 (CD105)), an accessory component of the receptor complex of transforming growth factor-β (TGF-β), has been developed for imaging of tumor neovasculature (1). 111In is a gamma emitter with a physical t½ of 2.8 days.

Because tumor growth and metastasis largely depend on angiogenesis, targeting of tumor vasculature is a promising strategy for cancer imaging and therapy (2). TGF-β is a pleiotropic cytokine that modulates angiogenesis, vascular remodeling, and tumor progression. Three isoforms of TGF-β, β1 to β3, have been identified. TGF-β1 appears to inhibit proliferation and migration of endothelial cells and their ability to form capillaries. CD105 (EDG) is a homodimeric cell membrane glycoprotein of 180 kDa, and it is a component of the TGF-β receptor complex that binds TGF-β1 and TGF-β3 with high affinity. CD105 is critical for correct blood vessel development. The expression of CD105 on different cells affects cellular response to TGF-β1. CD105 is overexpressed in proliferating endothelial cells of tumor vessels, and they prevent TGF-β1 inhibition of cellular proliferation (3, 4). Two isoforms of CD105, L and S, have been identified. L-CD105 is a protein of 633 amino acids and is expressed predominantly on endothelial cells. The molecular weight of CD105 is ~180,000 with disulfide-linked subunits of 95,000. The CD105 gene in humans has been mapped to chromosome 9q34→qter.

Radiolabeled MAbs have been developed for both the diagnosis and treatment of tumors (5-7). Quiescent human endothelial cells express CD105 only weakly, but the expression of CD105 is strongly up-regulated on the endothelium of tumor tissues undergoing angiogenesis (4). The high level of expressed CD105 (up to 106 molecules/proliferating cell) appears to be ideal for in vivo imaging and therapy. Tabata et al. (3) first investigated tumor targeting with 125I-labeled anti-CD105 MAbs in human breast tumor-bearing severe combined immune deficiency mice. The results showed the possible usefulness of antiangiogenic radioimmunotherapy with radiolabeled anti-CD105 MAbs. Anti-CD105 MAbs labeled with photon emitters can be used for tumor imaging. Fonsatti et al. (1) showed that a 125I-labeled anti-CD105 MAb (MAEND3) could efficiently image spontaneous mammary adenocarcinomas in two dogs. 125I is not an ideal radionuclide for imaging, but other radioactive iodines with better imaging properties are available. Alternatively, MAb can also be labeled with radiometals. Labeling with radiometals is generally achieved by indirect labeling with use of a bifunctional chelating agent (8, 9). 111In is considered one of the radionuclides of choice for antibody imaging studies. Bredow et al. (4) reported the successful preparation of 111In-labeled CD105-specific rat antimouse MAb MJ7/18 (IgG2a) as a potential molecular angiogenic marker.

Synthesis

[PubMed]

Bredow et al. (4) obtained CD105-specific rat antimouse MAb MJ7/18 (IgG2a) commercially and conjugated the antibody with diethylenetriaminepentaacetic acid (DTPA) cyclic anhydride. A 6-fold molar exces of DTPA cyclic anhydride per mole of antibody was reacted with dialyzed MJ7/18 MAb in borate buffer (pH 8.7) for 4 h (10). Nonreacted DTPA was removed by dialysis at 4 °C against 0.15 mM sodium citrate and 0.15 M sodium chloride (pH 6). 111In chloride in 50 mM hydrochloric acid was added to the DTPA-MAb solution and incubated for 1 h at room temperature. 111In-MJ7/18 MAb was purified by use of a size-exclusion Sephadex G-25m spin column.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

No publication is currently available.

Animal Studies

Rodents

[PubMed]

Bredow et al. (4) injected 5 μg (≤1.1 MBq (30 μCi)) of 111In-MJ7/18 into mice bearing the s.c. CD105-positive B16 melanoma for biodistribution and imaging studies. Immunohistology and autoradiography showed that the MAb bound to the extracellular domain of CD105. 111In-MJ7/18 MAb showed intense activity in the tumor periphery where the highest concentrations of vessels were found. Histologic analysis of higher power confirmed that the activity was maximally located on the endothelium of tumor vessels in the periphery of the sections. After i.v. injection of 111In-MJ7/18 MAb, radioactivity accumulated in tumors, and ~97% injected dose per g of the blood activity was removed from circulation within 15 min. Based on the single exponential decay model, the blood half-life (t½) was <1 min. Radioactivity bound to vascular endothelial cells in tissues of the liver, kidney, and heart. This mouse species showed higher expression of CD105 in these tissues compared with normal human organs. Radioactivity accumulation in percent injected dose per g (% ID/g) in the tumor vasculature (n = 4) occurred rapidly, with 0.75 ± 0.9, 1.69 ± 0.5, 1.67 ± 0.3, and 1.67 ± 0.7 at 2, 15, 60, and 360 min, respectively. In comparison, an 111In-nonspecific antibody (R35-95) accumulated slowly but reached the same radioactivity level at 60 min. The 111In-MJ7/18 radioactivity levels (% ID/g) of other major organs at 2 min were 2.45 ± 1.3 (blood), 3.17 ± 2.7 (heart), 0.30 ± 0.2 (kidney), 1.93 ± 2.4 (liver), and 2.54 ± 2.6 (lung), The radioactivity levels (% ID/g) at 60 min were 2.39 ± 0.1 (blood), 5.08 ± 1.2 (heart), 6.48 ± 3.8 (kidney), and 16.70 ± 2.6 (liver).

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.

References

1.
Fonsatti E. , Jekunen A.P. , Kairemo K.J. , Coral S. , Snellman M. , Nicotra M.R. , Natali P.G. , Altomonte M. , Maio M. Endoglin is a suitable target for efficient imaging of solid tumors: in vivo evidence in a canine mammary carcinoma model. Clin Cancer Res. 2000;6(5):2037–43. [PubMed: 10815930]
2.
Fonsatti E. , Altomonte M. , Arslan P. , Maio M. Endoglin (CD105): a target for anti-angiogenetic cancer therapy. Curr Drug Targets. 2003;4(4):291–6. [PubMed: 12699349]
3.
Tabata M. , Kondo M. , Haruta Y. , Seon B.K. Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using (125)I-labeled anti-endoglin monoclonal antibodies. Int J Cancer. 1999;82(5):737–42. [PubMed: 10417773]
4.
Bredow S. , Lewin M. , Hofmann B. , Marecos E. , Weissleder R. Imaging of tumour neovasculature by targeting the TGF-beta binding receptor endoglin. Eur J Cancer. 2000;36(5):675–81. [PubMed: 10738134]
5.
Wu A.M. , Senter P.D. Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol. 2005;23(9):1137–46. [PubMed: 16151407]
6.
Milenic D.E. , Brechbiel M.W. Targeting of radio-isotopes for cancer therapy. Cancer Biol Ther. 2004;3(4):361–70. [PubMed: 14976424]
7.
Kowalsky R.J. , Falen S.W. Radiopharmaceutcals in nuclear pharmacy and nuclear medicine. Second ed. , Washington, D.C.: APhA. 733-752. 2004
8.
Fritzberg A.R. , Berninger R.W. , Hadley S.W. , Wester D.W. Approaches to radiolabeling of antibodies for diagnosis and therapy of cancer. Pharm Res. 1988;5(6):325–34. [PubMed: 3072555]
9.
Hnatowich D.J. , Childs R.L. , Lanteigne D. , Najafi A. The preparation of DTPA-coupled antibodies radiolabeled with metallic radionuclides: an improved method. J Immunol Methods. 1983;65(1-2):147–57. [PubMed: 6655236]
10.
Marecos E. , Weissleder R. , Bogdanov A. Antibody-mediated versus nontargeted delivery in a human small cell lung carcinoma model. Bioconjug Chem. 1998;9(2):184–91. [PubMed: 9548533]

Views

Search MICAD

Limit my Search:


Related information

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...