Enhanced Tumor Targeting of Radiolabeled Mouse/Human Chimeric Anti-Tn Antibody in Losartan-Treated Mice Bearing Tn-Expressing Lung Tumors

• Published in: Cancer biotherapy & radiopharmaceuticals Vol. 39; no. 5; p. 337
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States 01-06-2024
• Subjects: Animals; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - pharmacology; Cell Line, Tumor; Female; Humans; Iodine Radioisotopes; Losartan - administration & dosage; Losartan - pharmacokinetics; Losartan - pharmacology; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Mice; Radiopharmaceuticals - pharmacokinetics; Radiopharmaceuticals - pharmacology; Technetium; Tissue Distribution; Tumor Protein, Translationally-Controlled 1; 99mTc; biodistribution; 131I; Chi-Tn; Losartan
• ISSN: 1557-8852
• DOI: 10.1089/cbr.2023.0138

ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (
I) and technetium-99m (
Tc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells.
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
Tc and
I showed different biodistribution patterns, with
Tc exhibiting higher values in the liver, spleen, and kidneys, while
I 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™
Tc.
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.