Comparative Radioimmunotherapy of Experimental Melanoma with Novel Humanized Antibody to Melanin Labeled with 213Bismuth and 177Lutetium
Melanoma is a cancer with increasing incidence and there is a need for alternatives to immunotherapy within effective approaches to treatment of metastatic melanoma. We performed comparative radioimmunotherapy (RIT) of experimental B16-F10 melanoma with novel humanized IgG to melanin h8C3 labeled wi...
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| Format: | Article |
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MDPI AG
2019-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/7/348 |
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| author | Kevin J. H. Allen Rubin Jiao Mackenzie E. Malo Connor Frank Darrell R. Fisher David Rickles Ekaterina Dadachova |
| author_facet | Kevin J. H. Allen Rubin Jiao Mackenzie E. Malo Connor Frank Darrell R. Fisher David Rickles Ekaterina Dadachova |
| author_sort | Kevin J. H. Allen |
| collection | DOAJ |
| description | Melanoma is a cancer with increasing incidence and there is a need for alternatives to immunotherapy within effective approaches to treatment of metastatic melanoma. We performed comparative radioimmunotherapy (RIT) of experimental B16-F10 melanoma with novel humanized IgG to melanin h8C3 labeled with a beta emitter, <sup>177</sup>Lu, and an alpha-emitter, <sup>213</sup>Bi, as well as biodistribution, microSPECT/CT imaging, and mouse and human dosimetry calculations. microSPECT/CT imaging showed that a humanized antibody that targets “free” melanin in the tumor microenvironment had high tumor uptake in B16F10 murine melanoma in C57Bl/6 mice, with little to no uptake in naturally melanized tissues. Extrapolation of the mouse dosimetry data to an adult human demonstrated that doses delivered to major organs and the whole body by <sup>177</sup>Lu-h8C3 would be approximately two times higher than those delivered by <sup>213</sup>Bi-h8C3, while the doses to the tumor would be almost similar. RIT results indicated that <sup>213</sup>Bi-h8C3 was more effective in slowing down the tumor growth than <sup>177</sup>Lu-h8C3, while both radiolabeled antibodies did not produce significant hematologic or systemic side effects. We concluded that h8C3 antibody labeled with <sup>213</sup>Bi is a promising reagent for translation into a clinical trial in patients with metastatic melanoma. |
| first_indexed | 2024-04-11T11:54:49Z |
| format | Article |
| id | doaj.art-fac8916038564d71940458814e0fa11a |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T11:54:49Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-fac8916038564d71940458814e0fa11a2022-12-22T04:25:12ZengMDPI AGPharmaceutics1999-49232019-07-0111734810.3390/pharmaceutics11070348pharmaceutics11070348Comparative Radioimmunotherapy of Experimental Melanoma with Novel Humanized Antibody to Melanin Labeled with 213Bismuth and 177LutetiumKevin J. H. Allen0Rubin Jiao1Mackenzie E. Malo2Connor Frank3Darrell R. Fisher4David Rickles5Ekaterina Dadachova6College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaVersant Medical Physics and Radiation Safety, Richland, WA 99354, USARadImmune Therapeutics, Tarrytown, NY 10591, USACollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaMelanoma is a cancer with increasing incidence and there is a need for alternatives to immunotherapy within effective approaches to treatment of metastatic melanoma. We performed comparative radioimmunotherapy (RIT) of experimental B16-F10 melanoma with novel humanized IgG to melanin h8C3 labeled with a beta emitter, <sup>177</sup>Lu, and an alpha-emitter, <sup>213</sup>Bi, as well as biodistribution, microSPECT/CT imaging, and mouse and human dosimetry calculations. microSPECT/CT imaging showed that a humanized antibody that targets “free” melanin in the tumor microenvironment had high tumor uptake in B16F10 murine melanoma in C57Bl/6 mice, with little to no uptake in naturally melanized tissues. Extrapolation of the mouse dosimetry data to an adult human demonstrated that doses delivered to major organs and the whole body by <sup>177</sup>Lu-h8C3 would be approximately two times higher than those delivered by <sup>213</sup>Bi-h8C3, while the doses to the tumor would be almost similar. RIT results indicated that <sup>213</sup>Bi-h8C3 was more effective in slowing down the tumor growth than <sup>177</sup>Lu-h8C3, while both radiolabeled antibodies did not produce significant hematologic or systemic side effects. We concluded that h8C3 antibody labeled with <sup>213</sup>Bi is a promising reagent for translation into a clinical trial in patients with metastatic melanoma.https://www.mdpi.com/1999-4923/11/7/348radioimmunotherapyhumanized antibodymelaninB16-F10 melanoma213Bismuth177Lutetium |
| spellingShingle | Kevin J. H. Allen Rubin Jiao Mackenzie E. Malo Connor Frank Darrell R. Fisher David Rickles Ekaterina Dadachova Comparative Radioimmunotherapy of Experimental Melanoma with Novel Humanized Antibody to Melanin Labeled with 213Bismuth and 177Lutetium Pharmaceutics radioimmunotherapy humanized antibody melanin B16-F10 melanoma 213Bismuth 177Lutetium |
| title | Comparative Radioimmunotherapy of Experimental Melanoma with Novel Humanized Antibody to Melanin Labeled with 213Bismuth and 177Lutetium |
| title_full | Comparative Radioimmunotherapy of Experimental Melanoma with Novel Humanized Antibody to Melanin Labeled with 213Bismuth and 177Lutetium |
| title_fullStr | Comparative Radioimmunotherapy of Experimental Melanoma with Novel Humanized Antibody to Melanin Labeled with 213Bismuth and 177Lutetium |
| title_full_unstemmed | Comparative Radioimmunotherapy of Experimental Melanoma with Novel Humanized Antibody to Melanin Labeled with 213Bismuth and 177Lutetium |
| title_short | Comparative Radioimmunotherapy of Experimental Melanoma with Novel Humanized Antibody to Melanin Labeled with 213Bismuth and 177Lutetium |
| title_sort | comparative radioimmunotherapy of experimental melanoma with novel humanized antibody to melanin labeled with 213bismuth and 177lutetium |
| topic | radioimmunotherapy humanized antibody melanin B16-F10 melanoma 213Bismuth 177Lutetium |
| url | https://www.mdpi.com/1999-4923/11/7/348 |
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