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OtherBASIC SCIENCE INVESTIGATIONS

Direct Procedure for the Production of 211At-Labeled Antibodies with an ε-Lysyl-3-(Trimethylstannyl)Benzamide Immunoconjugate

Sture Lindegren, Sofia Frost, Tom Bäck, Elin Haglund, Jörgen Elgqvist and Holger Jensen
Journal of Nuclear Medicine September 2008, 49 (9) 1537-1545; DOI: https://doi.org/10.2967/jnumed.107.049833
Sture Lindegren
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Sofia Frost
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Tom Bäck
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Elin Haglund
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Jörgen Elgqvist
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Holger Jensen
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  • FIGURE 1. 
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    FIGURE 1. 

    (A) Direct procedure. Conjugation of antibody (R-Lys-NH2) with m-MeATE and labeling of conjugated antibody. (B) Conventional procedure. Labeling of m-MeATE followed by conjugation of labeled reagent to antibody (R-Lys-NH2). SAB = N-succinimidyl 3-astatobenzoate.

  • FIGURE 2. 
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    FIGURE 2. 

    Tissue distribution of 211At after injection of 211At-trastuzumab labeled by direct procedure (□) and by conventional 2-step procedure (). Results are given as mean ± SD %IA/g. *Statistically significant difference (P < 0.05), as determined by Student t test.

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    TABLE 1

    Synthesis and Yields of 211At-Trastuzumab

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    TABLE 2

    Tissue Distribution Ratios After Coinjection in Mice of 211At-Trastuzumab Labeled by Direct Procedure and 125I-Trastuzumab Labeled by Conventional Procedure

    Tissue distribution ratio* at:
    Tissue1 h3 h6 h11 h24 h
    Blood0.98 ± 0.040.97 ± 0.020.96 ± 0.030.94 ± 0.020.89 ± 0.02
    Neck1.10 ± 0.041.18 ± 0.051.50 ± 0.151.15 ± 0.131.44 ± 0.21
    Salivary gland1.17 ± 0.041.29 ± 0.051.30 ± 0.031.25 ± 0.121.28 ± 0.13
    Heart1.06 ± 0.041.08 ± 0.031.06 ± 0.020.99 ± 0.020.97 ± 0.02
    Lung1.11 ± 0.051.14 ± 0.021.19 ± 0.061.09 ± 0.051.03 ± 0.08
    Liver1.03 ± 0.030.90 ± 0.090.95 ± 0.040.92 ± 0.080.78 ± 0.05
    Stomach1.29 ± 0.081.72 ± 0.072.36 ± 0.302.84 ± 0.661.88 ± 0.52
    Small intestine1.05 ± 0.051.03 ± 0.031.09 ± 0.061.03 ± 0.020.93 ± 0.09
    Large intestine1.06 ± 0.081.09 ± 0.021.13 ± 0.050.93 ± 0.030.93 ± 0.03
    Kidney1.00 ± 0.051.07 ± 0.011.09 ± 0.021.04 ± 0.010.98 ± 0.03
    Muscle1.05 ± 0.021.09 ± 0.021.09 ± 0.030.89 ± 0.080.87 ± 0.05
    Spleen1.03 ± 0.101.02 ± 0.111.13 ± 0.121.02 ± 0.060.83 ± 0.06
    • ↵* Results are given as mean ± SD (%IA/g for 211At/%IA/g for 125I) for 4 animals at each time point.

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    TABLE 3

    Tissue Distribution Ratios After Coinjection in Mice of 211At-Trastuzumab and 125I-Trastuzumab Labeled by Conventional Procedure

    Tissue distribution ratio* at:
    Tissue1 h3 h6 h11 h24 h
    Blood0.92 ± 0.020.91 ± 0.010.98 ± 0.041.01 ± 0.020.96 ± 0.02
    Neck1.03 ± 0.031.11 ± 0.081.40 ± 0.121.13 ± 0.071.48 ± 0.15
    Salivary gland1.14 ± 0.101.15 ± 0.111.28 ± 0.041.16 ± 0.071.18 ± 0.05
    Heart0.99 ± 0.010.98 ± 0.091.03 ± 0.041.02 ± 0.030.98 ± 0.03
    Lung1.03 ± 0.011.04 ± 0.031.11 ± 0.041.12 ± 0.051.06 ± 0.05
    Liver0.87 ± 0.030.87 ± 0.090.81 ± 0.030.84 ± 0.050.85 ± 0.06
    Stomach1.34 ± 0.062.03 ± 0.251.85 ± 0.182.12 ± 0.331.62 ± 0.15
    Small intestine0.99 ± 0.010.97 ± 0.030.97 ± 0.050.94 ± 0.090.94 ± 0.03
    Large intestine1.03 ± 0.051.06 ± 0.051.06 ± 0.060.93 ± 0.070.92 ± 0.08
    Kidney0.93 ± 0.010.96 ± 0.021.02 ± 0.021.03 ± 0.031.01 ± 0.01
    Muscle1.04 ± 0.051.08 ± 0.091.11 ± 0.040.96 ± 0.060.97 ± 0.04
    Spleen0.98 ± 0.050.98 ± 0.070.80 ± 0.040.82 ± 0.110.92 ± 0.08
    • ↵* Results are given as mean ± SD (%IA/g for 211At/%IA/g for 125I) for 4 animals at each time point.

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Journal of Nuclear Medicine: 49 (9)
Journal of Nuclear Medicine
Vol. 49, Issue 9
September 2008
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Direct Procedure for the Production of 211At-Labeled Antibodies with an ε-Lysyl-3-(Trimethylstannyl)Benzamide Immunoconjugate
Sture Lindegren, Sofia Frost, Tom Bäck, Elin Haglund, Jörgen Elgqvist, Holger Jensen
Journal of Nuclear Medicine Sep 2008, 49 (9) 1537-1545; DOI: 10.2967/jnumed.107.049833

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Direct Procedure for the Production of 211At-Labeled Antibodies with an ε-Lysyl-3-(Trimethylstannyl)Benzamide Immunoconjugate
Sture Lindegren, Sofia Frost, Tom Bäck, Elin Haglund, Jörgen Elgqvist, Holger Jensen
Journal of Nuclear Medicine Sep 2008, 49 (9) 1537-1545; DOI: 10.2967/jnumed.107.049833
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  • The Advantage of Antibody Cocktails for Targeted Alpha Therapy Depends on Specific Activity
  • Ex Vivo Activity Quantification in Micrometastases at the Cellular Scale Using the {alpha}-Camera Technique
  • Intraperitoneal {alpha}-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of 211At-MX35 F(ab')2--A Phase I Study
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