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High molecular mass radioimmunoconjugates are promising for intraperitoneal α-emitter immunotherapy due to prolonged retention in the peritoneum

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High molecular mass radioimmunoconjugates are promising for intraperitoneal α-emitter immunotherapy due to prolonged retention in the peritoneum

Auteurs : RBID : Pascal:12-0305199

Descripteurs français

Pascal (Inist)
- Carcinose péritonéale, Immunothérapie, Immunoradiothérapie, Intrapéritonéal, Traitement, Péritoine, Génie biomédical, Médecine nucléaire, Indium 111.
Wicri :
- concept : Médecine nucléaire.

English descriptors

KwdEn :
- Biomedical engineering, Immunoradiotherapy, Immunotherapy, Intraperitoneal, Nuclear medicine, Peritoneal carcinomatosis, Peritoneum, Treatment.

Abstract

Introduction: Therapeutic efficacy of intraperitoneal radioimmunotherapy is dependent on the time of retention of the radioimmunoconjugates within the peritoneal cavity. Therefore, the aim of this study was to investigate intraperitoneal retention of Fab, IgG and IgM radioimmunoconjugates. Methods: Female Balb/c mice were injected with ²¹³Bi- or ¹¹¹In-labeled IgM, IgG and recombinant Fab conjugates intraperitoneally or intravenously. At different time points after injection, whole body distribution of radionuclides was imaged using a gamma camera. Distribution of radionuclides in selected organs was determined via γ-counting after sacrifice. Biological half-lives of the conjugates were calculated from whole body activities. Results: After i.p. injection ²¹³Bi-Fab rapidly accumulated in the kidneys indicative of glomerular filtration and reabsorption. Accumulation of ²¹³Bi-IgG in the kidneys was significantly lower. ²¹³Bi-IgM showed a striking accumulation in the liver 180 min after i.p. injection. ¹¹¹In-IgG persisted in the circulation up to 72 h both after i.p. and i.v. injection. ¹¹¹In-IgM showed a continuous accumulation in the liver. Moreover, ¹¹¹In-IgM was significantly higher 24 h after i.v. injection than i.p. injection both in liver and spleen. These differences could be confirmed via scintigraphy. After injection of ¹¹¹In-IgG differences in scintigraphic images between i.v. and i.p. were clearly visible only at 3 h. Biological half lives were 24 h, 45 h and 165 h for ¹¹¹In-IgM, ¹¹¹In-Fab and ¹¹¹In-IgG, respectively. Conclusions: Retention of radioimmunoconjugates in the peritoneal cavity positively correlates with the molecular mass of the antibody. Therefore, IgM radioimmunoconjugates should be preferably used in radioimmunotherapy of free floating tumor cells and small tumor cell clusters in the ascites of the peritoneal cavity.

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Pascal:12-0305199

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<author><name sortKey="Rauch, Christian" uniqKey="Rauch C">Christian Rauch</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Nuclear Medicine, Technische Universität Miinchen</s1>
<s2>81675 Munich</s2>
<s3>DEU</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
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</author>
<author><name sortKey="Seidl, Christof" uniqKey="Seidl C">Christof Seidl</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Nuclear Medicine, Technische Universität Miinchen</s1>
<s2>81675 Munich</s2>
<s3>DEU</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schlapschy, Martin" uniqKey="Schlapschy M">Martin Schlapschy</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Lehrstuhl für Biologische Chemie, Technische Universität Miinchen</s1>
<s2>Freising-Weihenstephan</s2>
<s3>DEU</s3>
<sZ>3 aut.</sZ>
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<country>Allemagne</country>
<wicri:noRegion>Freising-Weihenstephan</wicri:noRegion>
<wicri:noRegion>Technische Universität Miinchen</wicri:noRegion>
<wicri:noRegion>Freising-Weihenstephan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Skerra, Arne" uniqKey="Skerra A">Arne Skerra</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Lehrstuhl für Biologische Chemie, Technische Universität Miinchen</s1>
<s2>Freising-Weihenstephan</s2>
<s3>DEU</s3>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<country>Allemagne</country>
<wicri:noRegion>Freising-Weihenstephan</wicri:noRegion>
<wicri:noRegion>Technische Universität Miinchen</wicri:noRegion>
<wicri:noRegion>Freising-Weihenstephan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Morgenstern, Alfred" uniqKey="Morgenstern A">Alfred Morgenstern</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>European Commission, Joint Research Centre, Institute for Transatranium Elements</s1>
<s2>Karlsruhe</s2>
<s3>DEU</s3>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Karlsruhe</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bruchertselfer, Frank" uniqKey="Bruchertselfer F">Frank Bruchertselfer</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>European Commission, Joint Research Centre, Institute for Transatranium Elements</s1>
<s2>Karlsruhe</s2>
<s3>DEU</s3>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Karlsruhe</settlement>
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<author><name sortKey="Senekowitsch Schmidtke, Reingard" uniqKey="Senekowitsch Schmidtke R">Reingard Senekowitsch-Schmidtke</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Nuclear Medicine, Technische Universität Miinchen</s1>
<s2>81675 Munich</s2>
<s3>DEU</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
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<date when="2012">2012</date>
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<title level="j" type="abbreviated">Nucl. med. biol.</title>
<title level="j" type="main">Nuclear medicine and biology</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biomedical engineering</term>
<term>Immunoradiotherapy</term>
<term>Immunotherapy</term>
<term>Intraperitoneal</term>
<term>Nuclear medicine</term>
<term>Peritoneal carcinomatosis</term>
<term>Peritoneum</term>
<term>Treatment</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Carcinose péritonéale</term>
<term>Immunothérapie</term>
<term>Immunoradiothérapie</term>
<term>Intrapéritonéal</term>
<term>Traitement</term>
<term>Péritoine</term>
<term>Génie biomédical</term>
<term>Médecine nucléaire</term>
<term>Indium 111</term>
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<front><div type="abstract" xml:lang="en">Introduction: Therapeutic efficacy of intraperitoneal radioimmunotherapy is dependent on the time of retention of the radioimmunoconjugates within the peritoneal cavity. Therefore, the aim of this study was to investigate intraperitoneal retention of Fab, IgG and IgM radioimmunoconjugates. Methods: Female Balb/c mice were injected with <sup>213</sup>
Bi- or <sup>111</sup>
In-labeled IgM, IgG and recombinant Fab conjugates intraperitoneally or intravenously. At different time points after injection, whole body distribution of radionuclides was imaged using a gamma camera. Distribution of radionuclides in selected organs was determined via γ-counting after sacrifice. Biological half-lives of the conjugates were calculated from whole body activities. Results: After i.p. injection <sup>213</sup>
Bi-Fab rapidly accumulated in the kidneys indicative of glomerular filtration and reabsorption. Accumulation of <sup>213</sup>
Bi-IgG in the kidneys was significantly lower. <sup>213</sup>
Bi-IgM showed a striking accumulation in the liver 180 min after i.p. injection. <sup>111</sup>
In-IgG persisted in the circulation up to 72 h both after i.p. and i.v. injection. <sup>111</sup>
In-IgM showed a continuous accumulation in the liver. Moreover, <sup>111</sup>
In-IgM was significantly higher 24 h after i.v. injection than i.p. injection both in liver and spleen. These differences could be confirmed via scintigraphy. After injection of <sup>111</sup>
In-IgG differences in scintigraphic images between i.v. and i.p. were clearly visible only at 3 h. Biological half lives were 24 h, 45 h and 165 h for <sup>111</sup>
In-IgM, <sup>111</sup>
In-Fab and <sup>111</sup>
In-IgG, respectively. Conclusions: Retention of radioimmunoconjugates in the peritoneal cavity positively correlates with the molecular mass of the antibody. Therefore, IgM radioimmunoconjugates should be preferably used in radioimmunotherapy of free floating tumor cells and small tumor cell clusters in the ascites of the peritoneal cavity.</div>
</front>
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<fA11 i1="01" i2="1"><s1>RAUCH (Christian)</s1>
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<fA11 i1="07" i2="1"><s1>SENEKOWITSCH-SCHMIDTKE (Reingard)</s1>
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<fA14 i1="01"><s1>Department of Nuclear Medicine, Technische Universität Miinchen</s1>
<s2>81675 Munich</s2>
<s3>DEU</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>7 aut.</sZ>
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<fA14 i1="02"><s1>Lehrstuhl für Biologische Chemie, Technische Universität Miinchen</s1>
<s2>Freising-Weihenstephan</s2>
<s3>DEU</s3>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>European Commission, Joint Research Centre, Institute for Transatranium Elements</s1>
<s2>Karlsruhe</s2>
<s3>DEU</s3>
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<sZ>6 aut.</sZ>
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<fC01 i1="01" l="ENG"><s0>Introduction: Therapeutic efficacy of intraperitoneal radioimmunotherapy is dependent on the time of retention of the radioimmunoconjugates within the peritoneal cavity. Therefore, the aim of this study was to investigate intraperitoneal retention of Fab, IgG and IgM radioimmunoconjugates. Methods: Female Balb/c mice were injected with <sup>213</sup>
Bi- or <sup>111</sup>
In-labeled IgM, IgG and recombinant Fab conjugates intraperitoneally or intravenously. At different time points after injection, whole body distribution of radionuclides was imaged using a gamma camera. Distribution of radionuclides in selected organs was determined via γ-counting after sacrifice. Biological half-lives of the conjugates were calculated from whole body activities. Results: After i.p. injection <sup>213</sup>
Bi-Fab rapidly accumulated in the kidneys indicative of glomerular filtration and reabsorption. Accumulation of <sup>213</sup>
Bi-IgG in the kidneys was significantly lower. <sup>213</sup>
Bi-IgM showed a striking accumulation in the liver 180 min after i.p. injection. <sup>111</sup>
In-IgG persisted in the circulation up to 72 h both after i.p. and i.v. injection. <sup>111</sup>
In-IgM showed a continuous accumulation in the liver. Moreover, <sup>111</sup>
In-IgM was significantly higher 24 h after i.v. injection than i.p. injection both in liver and spleen. These differences could be confirmed via scintigraphy. After injection of <sup>111</sup>
In-IgG differences in scintigraphic images between i.v. and i.p. were clearly visible only at 3 h. Biological half lives were 24 h, 45 h and 165 h for <sup>111</sup>
In-IgM, <sup>111</sup>
In-Fab and <sup>111</sup>
In-IgG, respectively. Conclusions: Retention of radioimmunoconjugates in the peritoneal cavity positively correlates with the molecular mass of the antibody. Therefore, IgM radioimmunoconjugates should be preferably used in radioimmunotherapy of free floating tumor cells and small tumor cell clusters in the ascites of the peritoneal cavity.</s0>
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High molecular mass radioimmunoconjugates are promising for intraperitoneal α-emitter immunotherapy due to prolonged retention in the peritoneum

High molecular mass radioimmunoconjugates are promising for intraperitoneal α-emitter immunotherapy due to prolonged retention in the peritoneum

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