Preclinical evaluation of early multi-organ toxicity induced by liposomal doxorubicin using 67Ga-citrate.

Nanotoxicology 2022 Mar

filter terms:

Although liposomal doxorubicin (LPD) is widely used for cancer treatment, knowledge concerning the toxicity induced by this drug in healthy organs and tissues is limited. LPD-induced toxicity studies relative to free doxorubicin (DOX) have focused on cardiotoxicity in tumor-bearing animals. On the other hand, the results on DOX-induced cardiotoxicity depending on gender are controversial. One of the manifestations of toxicity is tissue inflammation. 67Ga-citrate has been used for decades to assess inflammation in various pathologies. In this work, the ex vivo biodistribution of 67Ga-citrate is used to evaluate induced multi-organ toxicity in healthy 10-week-old male and female CD1 mice treated for 5 weeks with LPD. Toxicity in males, determined by 67Ga-citrate, was evident only in the target organs of liposomes (spleen, liver, kidneys, and lungs); the average weight loss was 11% and mortality was 14%. In female mice, 67Ga-citrate revealed a cytotoxic effect in practically all organs, the average weight loss was 37%, and the mortality after the last dose of LPD was 66%. These results confirm the usefulness of 67Ga-citrate and the importance of stratifying by sex in the toxicological evaluation of drugs.

Citation

Rigoberto Oros-Pantoja, Julio César Córdoba-Adaya, Eugenio Torres-García, Enrique Morales-Avila, Liliana Aranda-Lara, Jonnathan G Santillán-Benítez, Mariana Sánchez-Holguín, Neri O Hernández-Herrera, Gloria Otero, Keila Isaac-Olivé. Preclinical evaluation of early multi-organ toxicity induced by liposomal doxorubicin using 67Ga-citrate. Nanotoxicology. 2022 Mar;16(2):247-264