Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen

Abstract The clinical translation of theranostic 177Lu-radiopharmaceuticals based on inhibitors of the prostate-specific membrane antigen (PSMA) has demonstrated positive clinical responses in patients with advanced prostate cancer (PCa). However, challenges still remain, particularly regarding thei...

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Autores principales:	Debora Carpanese, Guillermina Ferro-Flores, Blanca Ocampo-Garcia, Clara Santos-Cuevas, Nicola Salvarese, Mariangela Figini, Giulio Fracasso, Laura De Nardo, Cristina Bolzati, Antonio Rosato, Laura Meléndez-Alafort
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b2d1ad6b66740dab5e3f6564255938b
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spelling	oai:doaj.org-article:9b2d1ad6b66740dab5e3f6564255938b2021-12-02T17:52:33ZDevelopment of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen10.1038/s41598-020-66285-22045-2322https://doaj.org/article/9b2d1ad6b66740dab5e3f6564255938b2020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-66285-2https://doaj.org/toc/2045-2322Abstract The clinical translation of theranostic 177Lu-radiopharmaceuticals based on inhibitors of the prostate-specific membrane antigen (PSMA) has demonstrated positive clinical responses in patients with advanced prostate cancer (PCa). However, challenges still remain, particularly regarding their pharmacokinetic and dosimetric properties. We developed a potential PSMA-immunotheranostic agent by conjugation of a single-chain variable fragment of the IgGD2B antibody (scFvD2B) to DOTA, to obtain a 177Lu-labelled agent with a better pharmacokinetic profile than those previously reported. The labelled conjugated 177Lu-scFvD2B was obtained in high yield and stability. In vitro, 177Lu-scFvD2B disclosed a higher binding and internalization in LNCaP (PSMA-positive) compared to PC3 (negative control) human PCa cells. In vivo studies in healthy nude mice revealed that 177Lu-scFvD2B present a favorable biokinetic profile, characterized by a rapid clearance from non-target tissues and minimal liver accumulation, but a slow wash-out from kidneys. Micro-SPECT/CT imaging of mice bearing pulmonary microtumors evidenced a slow uptake by LNCaP tumors, which steadily rose up to a maximum value of 3.6 SUV at 192 h. This high and prolonged tumor uptake suggests that 177Lu-scFvD2B has great potential in delivering ablative radiation doses to PSMA-expressing tumors, and warrants further studies to evaluate its preclinical therapeutic efficacy.Debora CarpaneseGuillermina Ferro-FloresBlanca Ocampo-GarciaClara Santos-CuevasNicola SalvareseMariangela FiginiGiulio FracassoLaura De NardoCristina BolzatiAntonio RosatoLaura Meléndez-AlafortNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Debora Carpanese Guillermina Ferro-Flores Blanca Ocampo-Garcia Clara Santos-Cuevas Nicola Salvarese Mariangela Figini Giulio Fracasso Laura De Nardo Cristina Bolzati Antonio Rosato Laura Meléndez-Alafort Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen
description	Abstract The clinical translation of theranostic 177Lu-radiopharmaceuticals based on inhibitors of the prostate-specific membrane antigen (PSMA) has demonstrated positive clinical responses in patients with advanced prostate cancer (PCa). However, challenges still remain, particularly regarding their pharmacokinetic and dosimetric properties. We developed a potential PSMA-immunotheranostic agent by conjugation of a single-chain variable fragment of the IgGD2B antibody (scFvD2B) to DOTA, to obtain a 177Lu-labelled agent with a better pharmacokinetic profile than those previously reported. The labelled conjugated 177Lu-scFvD2B was obtained in high yield and stability. In vitro, 177Lu-scFvD2B disclosed a higher binding and internalization in LNCaP (PSMA-positive) compared to PC3 (negative control) human PCa cells. In vivo studies in healthy nude mice revealed that 177Lu-scFvD2B present a favorable biokinetic profile, characterized by a rapid clearance from non-target tissues and minimal liver accumulation, but a slow wash-out from kidneys. Micro-SPECT/CT imaging of mice bearing pulmonary microtumors evidenced a slow uptake by LNCaP tumors, which steadily rose up to a maximum value of 3.6 SUV at 192 h. This high and prolonged tumor uptake suggests that 177Lu-scFvD2B has great potential in delivering ablative radiation doses to PSMA-expressing tumors, and warrants further studies to evaluate its preclinical therapeutic efficacy.
format	article
author	Debora Carpanese Guillermina Ferro-Flores Blanca Ocampo-Garcia Clara Santos-Cuevas Nicola Salvarese Mariangela Figini Giulio Fracasso Laura De Nardo Cristina Bolzati Antonio Rosato Laura Meléndez-Alafort
author_facet	Debora Carpanese Guillermina Ferro-Flores Blanca Ocampo-Garcia Clara Santos-Cuevas Nicola Salvarese Mariangela Figini Giulio Fracasso Laura De Nardo Cristina Bolzati Antonio Rosato Laura Meléndez-Alafort
author_sort	Debora Carpanese
title	Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen
title_short	Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen
title_full	Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen
title_fullStr	Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen
title_full_unstemmed	Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen
title_sort	development of 177lu-scfvd2b as a potential immunotheranostic agent for tumors overexpressing the prostate specific membrane antigen
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/9b2d1ad6b66740dab5e3f6564255938b
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Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen

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