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Enhanced Tumor Targeting of Radiolabeled Mouse/Human Chimeric Anti-Tn Antibody in Losartan-Treated Mice Bearing Tn-Expressing Lung Tumors.
Tassano, Marcos; Camacho, Ximena; Freire, Teresa; Perroni, Carolina; da Costa, Valeria; Cabrera, Mirel; García, Maria Fernanda; Fernandez, Marcelo; Gambini, Juan Pablo; Cabral, Pablo; Osinaga, Eduardo.
Afiliação
  • Tassano M; Area de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
  • Camacho X; Area de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
  • Freire T; Laboratorio de Inmunomodulacion y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay.
  • Perroni C; Area de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
  • da Costa V; Laboratorio de Inmunomodulacion y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay.
  • Cabrera M; Area de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
  • García MF; Area de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
  • Fernandez M; Area de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
  • Gambini JP; Centro de Medicina Nuclear e Imagenología Molecular, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
  • Cabral P; Area de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
  • Osinaga E; Laboratorio de Inmunomodulacion y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay.
Cancer Biother Radiopharm ; 39(5): 337-348, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38215243
ABSTRACT

Aim:

ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (131I) and technetium-99m (99mTc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells.

Results:

Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn- lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99mTc and 131I showed different biodistribution patterns, with 99mTc exhibiting higher values in the liver, spleen, and kidneys, while 131I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn- tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™99mTc.

Conclusions:

These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Losartan / Radioisótopos do Iodo / Neoplasias Pulmonares / Anticorpos Monoclonais Limite: Animals / Female / Humans Idioma: En Revista: Cancer Biother Radiopharm Assunto da revista: FARMACIA / FARMACOLOGIA / NEOPLASIAS / TERAPEUTICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Losartan / Radioisótopos do Iodo / Neoplasias Pulmonares / Anticorpos Monoclonais Limite: Animals / Female / Humans Idioma: En Revista: Cancer Biother Radiopharm Assunto da revista: FARMACIA / FARMACOLOGIA / NEOPLASIAS / TERAPEUTICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Estados Unidos