Evaluation of Actinium-225 Labeled Minigastrin Analogue [225Ac]Ac-DOTA-PP-F11N for Targeted Alpha Particle Therapy
| العنوان: | Evaluation of Actinium-225 Labeled Minigastrin Analogue [225Ac]Ac-DOTA-PP-F11N for Targeted Alpha Particle Therapy |
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| المؤلفون: | Stephan Frank, Alain Blanc, Michal Grzmil, Stefan Imobersteg, Roger Schibli, Martin Béhé, Yun Qin |
| المصدر: | Pharmaceutics, Vol 12, Iss 1088, p 1088 (2020) Pharmaceutics Volume 12 Issue 11 Pharmaceutics, 12 (11) |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Biodistribution, minigastrin analogue PP-F11N, lcsh:RS1-441, Pharmaceutical Science, actinium-225, Actinium-225, Cholecystokinin B receptor (CCKBR), Minigastrin analogue PP-F11N, Targeted alpha particle therapy (TAT), 030218 nuclear medicine & medical imaging, lcsh:Pharmacy and materia medica, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, targeted alpha particle therapy (TAT), medicine, DOTA, Cytotoxic T cell, business.industry, Cancer, medicine.disease, In vitro, cholecystokinin B receptor (CCKBR), chemistry, 030220 oncology & carcinogenesis, Cancer cell, Cholecystokinin B receptor, Cancer research, business, A431 cells |
| الوصف: | The overexpression of cholecystokinin B receptor (CCKBR) in human cancers led to the development of radiolabeled minigastrin analogues for targeted radionuclide therapy, which aims to deliver cytotoxic radiation specifically to cancer cells. Alpha emitters (e.g., actinium-225) possess high potency in cancer cell-killing and hold promise for the treatment of malignant tumors. In these preclinical studies, we developed and evaluated CCKBR-targeted alpha particle therapy. The cellular uptake and cytotoxic effect of actinium-225 labeled and HPLC-purified minigastrin analogue [225Ac]Ac-PP-F11N were characterized in the human squamous cancer A431 cells transfected with CCKBR. Nude mice bearing A431/CCKBR tumors were used for biodistribution and therapy studies followed by histological analysis and SPECT/CT imaging. In vitro, [225Ac]Ac-PP-F11N showed CCKBR-specific and efficient internalization rate and potent cytotoxicity. The biodistribution studies of [225Ac]Ac-PP-F11N revealed CCKBR-specific uptake in tumors, whereas the therapeutic studies demonstrated dose-dependent inhibition of tumor growth and extended mean survival time, without apparent toxicity. The histological analysis of kidney and stomach indicated no severe adverse effects after [225Ac]Ac-PP-F11N administration. The post-therapy SPECT-CT images with [111In]In-PP-F11N confirmed no CCKBR-positive tumor left in the mice with complete remission. In conclusion, our study demonstrates therapeutic efficacy of [225Ac]Ac-PP-F11N without acute radiotoxicity in CCKBR-positive cancer model. Pharmaceutics, 12 (11) |
| وصف الملف: | application/pdf; application/application/pdf |
| تدمد: | 1999-4923 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6397a4ffcd3f3807104467a1571c00baTest https://doi.org/10.3390/pharmaceutics12111088Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6397a4ffcd3f3807104467a1571c00ba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19994923 |
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