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Combination of Prot...
Combination of Proton Therapy and Radionuclide Therapy in Mice: Preclinical Pilot Study at the Paul Scherrer Institute
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Muller, C. (author)
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Leal, M. D. (author)
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Dominietto, M. D. (author)
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Umbricht, C. A. (author)
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Safai, S. (author)
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Perrin, R. L. (author)
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Egloff, M. (author)
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- Bernhardt, Peter, 1966 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för radiofysik,Institute of Clinical Sciences, Department of Radiation Physics
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van der Meulen, N. P. (author)
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Weber, D. C. (author)
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Schibli, R. (author)
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Lomax, A. J. (author)
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(creator_code:org_t)
- 2019-09-02
- 2019
- English.
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In: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 11:9
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https://www.mdpi.com...
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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Abstract
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- Proton therapy (PT) is a treatment with high dose conformality that delivers a highly-focused radiation dose to solid tumors. Targeted radionuclide therapy (TRT), on the other hand, is a systemic radiation therapy, which makes use of intravenously-applied radioconjugates. In this project, it was aimed to perform an initial dose-searching study for the combination of these treatment modalities in a preclinical setting. Therapy studies were performed with xenograft mouse models of folate receptor (FR)-positive KB and prostate-specific membrane antigen (PSMA)-positive PC-3 PIP tumors, respectively. PT and TRT using Lu-177-folate and Lu-177-PSMA-617, respectively, were applied either as single treatments or in combination. Monitoring of the mice over nine weeks revealed a similar tumor growth delay after PT and TRT, respectively, when equal tumor doses were delivered either by protons or by beta over bar -particles, respectively. Combining the methodologies to provide half-dose by either therapy approach resulted in equal (PC-3 PIP tumor model) or even slightly better therapy outcomes (KB tumor model). In separate experiments, preclinical positron emission tomography (PET) was performed to investigate tissue activation after proton irradiation of the tumor. The high-precision radiation delivery of PT was confirmed by the resulting PET images that accurately visualized the irradiated tumor tissue. In this study, the combination of PT and TRT resulted in an additive effect or a trend of synergistic effects, depending on the type of tumor xenograft. This study laid the foundation for future research regarding therapy options in the situation of metastasized solid tumors, where surgery or PT alone are not a solution but may profit from combination with systemic radiation therapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Klinisk vetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Clinical Science (hsv//eng)
Keyword
- proton therapy
- targeted radionuclide therapy
- PET imaging
- folate receptor
- PSMA
- Lu-177
- long-term outcomes
- beam therapy
- tumor-therapy
- radiotherapy
- cancer
- radioimmunotherapy
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Muller, C.
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Leal, M. D.
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Dominietto, M. D ...
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Umbricht, C. A.
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Safai, S.
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Perrin, R. L.
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show more...
-
Egloff, M.
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Bernhardt, Peter ...
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van der Meulen, ...
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Weber, D. C.
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Schibli, R.
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Lomax, A. J.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- AGRICULTURAL SCIENCES
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AGRICULTURAL SCI ...
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and Veterinary Scien ...
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and Clinical Science
- Articles in the publication
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Pharmaceutics
- By the university
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University of Gothenburg