Tumor Retention of super(186)Re-MAG3, super(111)In-DTPA and super(125)I Labeled Monoclonal Antibody G250 in Nude Mice with Renal Cell Carcinoma Xenografts

Tumor Retention of super(186)Re-MAG3, super(111)In-DTPA and super(125)I Labeled Monoclonal Antibody G250 in Nude Mice with Renal Cell Carcinoma Xenografts

In radioimmunotherapy of solid tumors substantial gain might be achieved by carefully selecting the radionuclide and the linker connecting it to the antibody. In contrast to super(131)I, radiometals such as super(90)Y and super(111)In may be retained in the tumor cell after internalization of the an...

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Veröffentlicht in:Cancer biotherapy & radiopharmaceuticals 1998-04, Vol.13 (2), p.133-139
Hauptverfasser: Steffens, M G, Kranenborg, MHGC, Boerman, O C, Zegwaart-Hagemeier, NEM, Debruyne, FMJ, Corstens, FHM, Oosterwijk, E
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container_end_page 139
container_issue 2
container_start_page 133
container_title Cancer biotherapy & radiopharmaceuticals
container_volume 13
creator Steffens, M G
Kranenborg, MHGC
Boerman, O C
Zegwaart-Hagemeier, NEM
Debruyne, FMJ
Corstens, FHM
Oosterwijk, E
description In radioimmunotherapy of solid tumors substantial gain might be achieved by carefully selecting the radionuclide and the linker connecting it to the antibody. In contrast to super(131)I, radiometals such as super(90)Y and super(111)In may be retained in the tumor cell after internalization of the antibody, thereby enhancing the radiation dose to the tumor. The physical properties of super(186)Re with 1.08 MeV beta -emission (71%) and 137 keV gamma -emission (10 %) seem ideal for radioimmunotherapy. In this study we investigated in nude mice with s.c. renal cell carcinoma xenografts the biodistribution and the retention in the tumor of super(186)Re-MAG3 labeled monoclonal antibody (mAb) G250 as compared to super(111)In-DTPA-G250, to super(125)I-G250 and to super(131)I-MN14 (non-specific control mAb). Radiolabeled antibody preparations were i.v. injected. Seventy two hours p.i. the biodistribution of the radiolabel was determined. Blood levels of all mAb G250 preparations were remarkably low (mean: 2.38, 1.40 and 1.43 %ID/g for super(125)I, super(111)In and super(186)Re respectively) whereas blood levels of mAb MN14 were significantly higher (mean: 12.3 %ID/g), indicating tumor processing of mAb G250. Retention of super(111)In in the tumor was significantly higher than of super(186)Re and super(125)I whereas retention in the tumor of super(186)Re and super(125)I did not differ significantly. Conclusion: In contrast to other radiometals such as super(111)In and super(90)Y, super(186)Re is not retained in the tumor cell. Therefore super(186)Re has no additional advantage for radioimmunotherapy with respect to retention in the tumor.
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In contrast to super(131)I, radiometals such as super(90)Y and super(111)In may be retained in the tumor cell after internalization of the antibody, thereby enhancing the radiation dose to the tumor. The physical properties of super(186)Re with 1.08 MeV beta -emission (71%) and 137 keV gamma -emission (10 %) seem ideal for radioimmunotherapy. In this study we investigated in nude mice with s.c. renal cell carcinoma xenografts the biodistribution and the retention in the tumor of super(186)Re-MAG3 labeled monoclonal antibody (mAb) G250 as compared to super(111)In-DTPA-G250, to super(125)I-G250 and to super(131)I-MN14 (non-specific control mAb). Radiolabeled antibody preparations were i.v. injected. Seventy two hours p.i. the biodistribution of the radiolabel was determined. Blood levels of all mAb G250 preparations were remarkably low (mean: 2.38, 1.40 and 1.43 %ID/g for super(125)I, super(111)In and super(186)Re respectively) whereas blood levels of mAb MN14 were significantly higher (mean: 12.3 %ID/g), indicating tumor processing of mAb G250. Retention of super(111)In in the tumor was significantly higher than of super(186)Re and super(125)I whereas retention in the tumor of super(186)Re and super(125)I did not differ significantly. Conclusion: In contrast to other radiometals such as super(111)In and super(90)Y, super(186)Re is not retained in the tumor cell. 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Blood levels of all mAb G250 preparations were remarkably low (mean: 2.38, 1.40 and 1.43 %ID/g for super(125)I, super(111)In and super(186)Re respectively) whereas blood levels of mAb MN14 were significantly higher (mean: 12.3 %ID/g), indicating tumor processing of mAb G250. Retention of super(111)In in the tumor was significantly higher than of super(186)Re and super(125)I whereas retention in the tumor of super(186)Re and super(125)I did not differ significantly. Conclusion: In contrast to other radiometals such as super(111)In and super(90)Y, super(186)Re is not retained in the tumor cell. 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In contrast to super(131)I, radiometals such as super(90)Y and super(111)In may be retained in the tumor cell after internalization of the antibody, thereby enhancing the radiation dose to the tumor. The physical properties of super(186)Re with 1.08 MeV beta -emission (71%) and 137 keV gamma -emission (10 %) seem ideal for radioimmunotherapy. In this study we investigated in nude mice with s.c. renal cell carcinoma xenografts the biodistribution and the retention in the tumor of super(186)Re-MAG3 labeled monoclonal antibody (mAb) G250 as compared to super(111)In-DTPA-G250, to super(125)I-G250 and to super(131)I-MN14 (non-specific control mAb). Radiolabeled antibody preparations were i.v. injected. Seventy two hours p.i. the biodistribution of the radiolabel was determined. Blood levels of all mAb G250 preparations were remarkably low (mean: 2.38, 1.40 and 1.43 %ID/g for super(125)I, super(111)In and super(186)Re respectively) whereas blood levels of mAb MN14 were significantly higher (mean: 12.3 %ID/g), indicating tumor processing of mAb G250. Retention of super(111)In in the tumor was significantly higher than of super(186)Re and super(125)I whereas retention in the tumor of super(186)Re and super(125)I did not differ significantly. Conclusion: In contrast to other radiometals such as super(111)In and super(90)Y, super(186)Re is not retained in the tumor cell. Therefore super(186)Re has no additional advantage for radioimmunotherapy with respect to retention in the tumor.</abstract></addata></record>
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title Tumor Retention of super(186)Re-MAG3, super(111)In-DTPA and super(125)I Labeled Monoclonal Antibody G250 in Nude Mice with Renal Cell Carcinoma Xenografts
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