Thiago Goulart Rosa1, Sofia Nascimento Dos Santos1, Terezina de Jesus Andreoli Pinto2, Daniele Dal Molim Ghisleni2, Thereza Christina Barja-Fidalgo3, Eduardo Ricci-Junior4, Mohammed Al-Qahtani5, Jan Kozempel6, Emerson Soares Bernardes7, Ralph Santos-Oliveira8. 1. Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro, Brazil. 2. Faculty of Pharmaceutical Sciences,, University of São Paulo, São Paulo, SP, Brazil. 3. Laboratory of Molecular and Cellular Pharmacology; Department of Cell Biology, Institute of Biology Roberto Alcântara Gomes, Biomedical Center, State University of Rio de Janeiro,, Rio de Janeiro, RJ, Brazil. 4. Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 5. Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. 6. Katedra jaderné chemie, FJFI ČVUT v Praze, Prague, Czech Republic. 7. Centro de Radiofarmácia, Instituto de Pesquisas Energéticas e Nucleares, São Paulo, Brazil. 8. Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro, Brazil. presidenciaradiofarmacia@gmail.com.
Abstract
PURPOSE: The purpose of this article was to develop, characterize and test (in vivo) dacarbazine microparticles that may be labeled with 99mTc and Ra-223 for both use: diagnostic and therapy of metastatic melanoma. METHODS: We developed by double emulsion solvent evaporation methodology the microparticle. The characterization has been done using, Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). The labeling with 99mTc and Ra-223 has been done by the direct labeling process. Also the formulation has been tested pre-clinically using Balb/c mice inducted with melanoma, performing the the biodistribution and planar imaging. Cytotoxicity evaluation was also done in M3 V cell line. In order to understand the safety aspects of the microparticles, microbiological study (endotoxin and sterility) has been done. Finally, planar imaging was performed to evaluate the diagnosing aspect. RESULTS: The results showed that a 559 nm microparticles was obtained with a spherical shape. The labeling process with 99mTc reached over 90% of efficacy. On the other hand, the labeling process with Ra-223 showed a 70% efficacy. The results in inducted animals demonstrated that the microparticles were able to reach the tumor with a high rate (20%). Also demonstrated a low recognition by the Mononuclear Phagocytic System. The cytotoxicity and the microbiological control, corroborates the safety aspect of these microparticles. CONCLUSION: The planar image and the possible labeling with Ra-223, corroborates the use as a theragnostic agent for imaging and therapy of Metastatic Melanoma.
PURPOSE: The purpose of this article was to develop, characterize and test (in vivo) dacarbazine microparticles that may be labeled with 99mTc and Ra-223 for both use: diagnostic and therapy of metastatic melanoma. METHODS: We developed by double emulsion solvent evaporation methodology the microparticle. The characterization has been done using, Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). The labeling with 99mTc and Ra-223 has been done by the direct labeling process. Also the formulation has been tested pre-clinically using Balb/c mice inducted with melanoma, performing the the biodistribution and planar imaging. Cytotoxicity evaluation was also done in M3 V cell line. In order to understand the safety aspects of the microparticles, microbiological study (endotoxin and sterility) has been done. Finally, planar imaging was performed to evaluate the diagnosing aspect. RESULTS: The results showed that a 559 nm microparticles was obtained with a spherical shape. The labeling process with 99mTc reached over 90% of efficacy. On the other hand, the labeling process with Ra-223 showed a 70% efficacy. The results in inducted animals demonstrated that the microparticles were able to reach the tumor with a high rate (20%). Also demonstrated a low recognition by the Mononuclear Phagocytic System. The cytotoxicity and the microbiological control, corroborates the safety aspect of these microparticles. CONCLUSION: The planar image and the possible labeling with Ra-223, corroborates the use as a theragnostic agent for imaging and therapy of Metastatic Melanoma.
Authors: Suyene Rocha Pinto; Michelle Alvares Sarcinelle; Marta de Souza Albernaz; Franciana Maria Rosa da Silva; Sergio Henrique Seabra; Patricia Almeida do Nascimento; Cosme Leonardo Gomes Carvalho; Ralph Santos-Oliveira Journal: Nucl Med Biol Date: 2014-06-02 Impact factor: 2.408
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396
Authors: Cristiane Ribeiro-Pereira; João Alfredo Moraes; Mariele de Jesus Souza; Francisco R Laurindo; Maria Augusta Arruda; Christina Barja-Fidalgo Journal: PLoS One Date: 2014-06-09 Impact factor: 3.240
Authors: Sara Rhaissa Rezende Dos Reis; Suyene Rocha Pinto; Frederico Duarte de Menezes; Ramon Martinez-Manez; Eduardo Ricci-Junior; Luciana Magalhaes Rebelo Alencar; Edward Helal-Neto; Aline Oiveira da Silva de Barros; Patricia Cristina Lisboa; Ralph Santos-Oliveira Journal: Pharm Res Date: 2020-01-22 Impact factor: 4.200
Authors: Edward Helal-Neto; Aline Oliveira da Silva de Barros; Roberta Saldanha-Gama; Renata Brandão-Costa; Luciana Magalhães Rebêlo Alencar; Clenilton Costa Dos Santos; Ramón Martínez-Máñez; Eduardo Ricci-Junior; Frank Alexis; Verônica Morandi; Christina Barja-Fidalgo; Ralph Santos-Oliveira Journal: Int J Mol Sci Date: 2019-12-28 Impact factor: 5.923