Enhanced tumor targeting of radiolabeled mouse/human chimeric anti-Tn antibody in losartan-treated mice bearing Tn-expressing lung tumors

Abstract

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. 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 131 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-HYNIC99mTc. These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartantreated 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.