Safety evaluation of very high doses of intravitreal topotecan in rabbits

Autores
del Sole, Maria Jose; Nejamkin, Pablo; Clausse, María; Farall, Rodolfo Andres; Chan, Débora; Lamas, Gabriela; Lubieniecki, Fabiana; Schaiquevich, Paula Susana; Abramson, David
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Introduction Intravitreal topotecan (TPT) at 90 μg has shown promise for treating intraocular retinoblastoma. However, the control of refractory or recurrent vitreous seeds and retinal tumors remains a challenge and these difficult-to-treat eyes may require higher doses than those currently used in the clinic. Objectives To evaluate systemic and ocular safety of monthly very high-doses intravitreal injections of TPT in rabbits. Methods Systemic and ocular toxicity was assessed in non-tumor-bearing New Zealand rabbits after three monthly intravitreal injections of sterile water, 50 μg, 100 μg or 200 μg of TPT into one eye and vehicle into the contralateral. Animals were evaluated monthly for general and ophthalmic clinical status including direct and indirect ophthalmoscopy, biomicroscopy, and scotopic electroretinography (ERG). One month after the last injection, the eyes were enucleated and subjected to histological assessment. Linear mixed effects models were used for the statistical analysis of the treatment effects. Results Weight, hair loss, or changes in hematologic values were absent during the study period across all animal groups. No evidence of retinal or optic nerve alterations were evidenced by fundus examination except in 2 eyes treated with 200 μg TPT that showed attenuation of retinal vasculature. Histological examination revealed no distinct abnormalities except for one eye treated with 200 μg TPT that showed a focus area of retinal distortion with loss of photoreceptors and gliosis. In line, a significant decrease in the a- and b-wave amplitudes of the ERG recording was registered for the group of eyes treated with 200 μg TPT despite ERG parameters remained within normal values for visual function. Conclusion Intravitreal TPT up to 100 μg per dose was safe in the rabbit’s eye. The results suggest a promising potential for clinical application of doses up to 200 μg TPT in relapse/refractory cases of retinoblastoma.
Fil: del Sole, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Nejamkin, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Clausse, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Farall, Rodolfo Andres. Universidad de Buenos Aires. Facultad de Ingeniería; Argentina
Fil: Chan, Débora. Universidad Austral. Facultad de Ingeniería; Argentina
Fil: Lamas, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina
Fil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina
Fil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Abramson, David. Memorial Sloan-Kettering Cancer Center; Estados Unidos
XXVI Biennial Meeting of the International Society for Eye Research
Ciudad Autónoma de Buenos Aires
Argentina
International Society for Eye Research
Materia
Retinoblastoma
Safety evaluation
Retinoblastoma
Rabbits
Intravitreal topotecan
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/258365
Acceder
id CONICETDig_2c143f16784af3262fd8adb1b0b29f4f
oai_identifier_str oai:ri.conicet.gov.ar:11336/258365
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Safety evaluation of very high doses of intravitreal topotecan in rabbitsdel Sole, Maria JoseNejamkin, PabloClausse, MaríaFarall, Rodolfo AndresChan, DéboraLamas, GabrielaLubieniecki, FabianaSchaiquevich, Paula SusanaAbramson, DavidRetinoblastomaSafety evaluationRetinoblastomaRabbitsIntravitreal topotecanhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Introduction Intravitreal topotecan (TPT) at 90 μg has shown promise for treating intraocular retinoblastoma. However, the control of refractory or recurrent vitreous seeds and retinal tumors remains a challenge and these difficult-to-treat eyes may require higher doses than those currently used in the clinic. Objectives To evaluate systemic and ocular safety of monthly very high-doses intravitreal injections of TPT in rabbits. Methods Systemic and ocular toxicity was assessed in non-tumor-bearing New Zealand rabbits after three monthly intravitreal injections of sterile water, 50 μg, 100 μg or 200 μg of TPT into one eye and vehicle into the contralateral. Animals were evaluated monthly for general and ophthalmic clinical status including direct and indirect ophthalmoscopy, biomicroscopy, and scotopic electroretinography (ERG). One month after the last injection, the eyes were enucleated and subjected to histological assessment. Linear mixed effects models were used for the statistical analysis of the treatment effects. Results Weight, hair loss, or changes in hematologic values were absent during the study period across all animal groups. No evidence of retinal or optic nerve alterations were evidenced by fundus examination except in 2 eyes treated with 200 μg TPT that showed attenuation of retinal vasculature. Histological examination revealed no distinct abnormalities except for one eye treated with 200 μg TPT that showed a focus area of retinal distortion with loss of photoreceptors and gliosis. In line, a significant decrease in the a- and b-wave amplitudes of the ERG recording was registered for the group of eyes treated with 200 μg TPT despite ERG parameters remained within normal values for visual function. Conclusion Intravitreal TPT up to 100 μg per dose was safe in the rabbit’s eye. The results suggest a promising potential for clinical application of doses up to 200 μg TPT in relapse/refractory cases of retinoblastoma.Fil: del Sole, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Nejamkin, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Clausse, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Farall, Rodolfo Andres. Universidad de Buenos Aires. Facultad de Ingeniería; ArgentinaFil: Chan, Débora. Universidad Austral. Facultad de Ingeniería; ArgentinaFil: Lamas, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; ArgentinaFil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Abramson, David. Memorial Sloan-Kettering Cancer Center; Estados UnidosXXVI Biennial Meeting of the International Society for Eye ResearchCiudad Autónoma de Buenos AiresArgentinaInternational Society for Eye ResearchInternational Society for Eye Research2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/258365Safety evaluation of very high doses of intravitreal topotecan in rabbits; XXVI Biennial Meeting of the International Society for Eye Research; Ciudad Autónoma de Buenos Aires; Argentina; 2024; 562-562CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://react-profile.org/ebook/ISER2024_AbstractBook/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:10Zoai:ri.conicet.gov.ar:11336/258365instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:07:11.121CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Safety evaluation of very high doses of intravitreal topotecan in rabbits
title Safety evaluation of very high doses of intravitreal topotecan in rabbits
spellingShingle Safety evaluation of very high doses of intravitreal topotecan in rabbits
del Sole, Maria Jose
Retinoblastoma
Safety evaluation
Retinoblastoma
Rabbits
Intravitreal topotecan
title_short Safety evaluation of very high doses of intravitreal topotecan in rabbits
title_full Safety evaluation of very high doses of intravitreal topotecan in rabbits
title_fullStr Safety evaluation of very high doses of intravitreal topotecan in rabbits
title_full_unstemmed Safety evaluation of very high doses of intravitreal topotecan in rabbits
title_sort Safety evaluation of very high doses of intravitreal topotecan in rabbits
dc.creator.none.fl_str_mv del Sole, Maria Jose
Nejamkin, Pablo
Clausse, María
Farall, Rodolfo Andres
Chan, Débora
Lamas, Gabriela
Lubieniecki, Fabiana
Schaiquevich, Paula Susana
Abramson, David
author del Sole, Maria Jose
author_facet del Sole, Maria Jose
Nejamkin, Pablo
Clausse, María
Farall, Rodolfo Andres
Chan, Débora
Lamas, Gabriela
Lubieniecki, Fabiana
Schaiquevich, Paula Susana
Abramson, David
author_role author
author2 Nejamkin, Pablo
Clausse, María
Farall, Rodolfo Andres
Chan, Débora
Lamas, Gabriela
Lubieniecki, Fabiana
Schaiquevich, Paula Susana
Abramson, David
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Retinoblastoma
Safety evaluation
Retinoblastoma
Rabbits
Intravitreal topotecan
topic Retinoblastoma
Safety evaluation
Retinoblastoma
Rabbits
Intravitreal topotecan
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Introduction Intravitreal topotecan (TPT) at 90 μg has shown promise for treating intraocular retinoblastoma. However, the control of refractory or recurrent vitreous seeds and retinal tumors remains a challenge and these difficult-to-treat eyes may require higher doses than those currently used in the clinic. Objectives To evaluate systemic and ocular safety of monthly very high-doses intravitreal injections of TPT in rabbits. Methods Systemic and ocular toxicity was assessed in non-tumor-bearing New Zealand rabbits after three monthly intravitreal injections of sterile water, 50 μg, 100 μg or 200 μg of TPT into one eye and vehicle into the contralateral. Animals were evaluated monthly for general and ophthalmic clinical status including direct and indirect ophthalmoscopy, biomicroscopy, and scotopic electroretinography (ERG). One month after the last injection, the eyes were enucleated and subjected to histological assessment. Linear mixed effects models were used for the statistical analysis of the treatment effects. Results Weight, hair loss, or changes in hematologic values were absent during the study period across all animal groups. No evidence of retinal or optic nerve alterations were evidenced by fundus examination except in 2 eyes treated with 200 μg TPT that showed attenuation of retinal vasculature. Histological examination revealed no distinct abnormalities except for one eye treated with 200 μg TPT that showed a focus area of retinal distortion with loss of photoreceptors and gliosis. In line, a significant decrease in the a- and b-wave amplitudes of the ERG recording was registered for the group of eyes treated with 200 μg TPT despite ERG parameters remained within normal values for visual function. Conclusion Intravitreal TPT up to 100 μg per dose was safe in the rabbit’s eye. The results suggest a promising potential for clinical application of doses up to 200 μg TPT in relapse/refractory cases of retinoblastoma.
Fil: del Sole, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Nejamkin, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Clausse, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Farall, Rodolfo Andres. Universidad de Buenos Aires. Facultad de Ingeniería; Argentina
Fil: Chan, Débora. Universidad Austral. Facultad de Ingeniería; Argentina
Fil: Lamas, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina
Fil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina
Fil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Abramson, David. Memorial Sloan-Kettering Cancer Center; Estados Unidos
XXVI Biennial Meeting of the International Society for Eye Research
Ciudad Autónoma de Buenos Aires
Argentina
International Society for Eye Research
description Introduction Intravitreal topotecan (TPT) at 90 μg has shown promise for treating intraocular retinoblastoma. However, the control of refractory or recurrent vitreous seeds and retinal tumors remains a challenge and these difficult-to-treat eyes may require higher doses than those currently used in the clinic. Objectives To evaluate systemic and ocular safety of monthly very high-doses intravitreal injections of TPT in rabbits. Methods Systemic and ocular toxicity was assessed in non-tumor-bearing New Zealand rabbits after three monthly intravitreal injections of sterile water, 50 μg, 100 μg or 200 μg of TPT into one eye and vehicle into the contralateral. Animals were evaluated monthly for general and ophthalmic clinical status including direct and indirect ophthalmoscopy, biomicroscopy, and scotopic electroretinography (ERG). One month after the last injection, the eyes were enucleated and subjected to histological assessment. Linear mixed effects models were used for the statistical analysis of the treatment effects. Results Weight, hair loss, or changes in hematologic values were absent during the study period across all animal groups. No evidence of retinal or optic nerve alterations were evidenced by fundus examination except in 2 eyes treated with 200 μg TPT that showed attenuation of retinal vasculature. Histological examination revealed no distinct abnormalities except for one eye treated with 200 μg TPT that showed a focus area of retinal distortion with loss of photoreceptors and gliosis. In line, a significant decrease in the a- and b-wave amplitudes of the ERG recording was registered for the group of eyes treated with 200 μg TPT despite ERG parameters remained within normal values for visual function. Conclusion Intravitreal TPT up to 100 μg per dose was safe in the rabbit’s eye. The results suggest a promising potential for clinical application of doses up to 200 μg TPT in relapse/refractory cases of retinoblastoma.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/258365
Safety evaluation of very high doses of intravitreal topotecan in rabbits; XXVI Biennial Meeting of the International Society for Eye Research; Ciudad Autónoma de Buenos Aires; Argentina; 2024; 562-562
CONICET Digital
CONICET
url http://hdl.handle.net/11336/258365
identifier_str_mv Safety evaluation of very high doses of intravitreal topotecan in rabbits; XXVI Biennial Meeting of the International Society for Eye Research; Ciudad Autónoma de Buenos Aires; Argentina; 2024; 562-562
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://react-profile.org/ebook/ISER2024_AbstractBook/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv International Society for Eye Research
publisher.none.fl_str_mv International Society for Eye Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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