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Characteristics of Ibritumomab as Radionuclide Therapy Agent

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Resistance to Ibritumomab in Lymphoma

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 18))

Abstract

Ibritumomab tiuxetan was approved by the FDA as the first radiolabeled monoclonal antibody (mAb) for radioimmunotherapy (RIT: a selective internal radiation therapy using radioisotopes conjugated to tumor-directed antibodies or those fragments) in early 2002 and is now widely used for the treatment of B-cell non-Hodgkin’s lymphoma (NHL). This pharmaceutical agent consists of the murine anti-CD20 chimeric IgG1 mAb, ibritumomab, which is covalently conjugated with the chelator tiuxetan, permitting stable binding to metal cations. In the clinic, two kinds of radioisotopes can be coupled to ibritumomab tiuxetan, namely 111In for cancer imaging and 90Y for the targeted cytotoxic therapy. Dual-label protocols (confirmation of the appropriate mAb distribution using 111In-ibritumomab tiuxetan, followed by radiotherapy by 90Y-ibritumomab tiuxetan) can lead to the effective RIT. To better understand how these radiopharmaceuticals achieve “theranostics” (a combination of diagnosis and therapy) against B-cell NHL, the pharmaceutical characteristics of 90Y-/111In-conjugated ibritumomab tiuxetan are outlined in this chapter.

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Abbreviations

%ID/g:

% injected dose per gram of tissue

111In:

Indium-111

90Y:

Yttrium-90

ADCC:

Antibody-dependent cellular cytotoxicity

CDC:

Complement-dependent cytotoxicity

DTPA:

Diethylenetriaminepentaacetic acid

HAMA:

Human antimurine antibody

K d :

Dissociation constant

mAb:

Monoclonal antibody

MIRD:

Medical Internal Radiation Dose

NHL:

Non-Hodgkin’s lymphoma

PET:

Positron emission tomography

RIT:

Radioimmunotherapy

SPECT:

Single-photon emission computed tomography

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Authors and Affiliations

  1. Radioisotope Research Center, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan

    Hidekazu Kawashima

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  1. Hidekazu Kawashima
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Correspondence to Hidekazu Kawashima .

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  1. Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan

    Makoto Hosono

  2. GIP Arronax, Nantes-Saint-Herblain, France

    Jean-François Chatal

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Kawashima, H. (2018). Characteristics of Ibritumomab as Radionuclide Therapy Agent. In: Hosono, M., Chatal, JF. (eds) Resistance to Ibritumomab in Lymphoma. Resistance to Targeted Anti-Cancer Therapeutics, vol 18. Springer, Cham. https://doi.org/10.1007/978-3-319-78238-6_6

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