Evaluation of doxorubicin-induced early multi-organ toxicity in male CD1 mice by biodistribution of ¹⁸F-FDG and ⁶⁷Ga-citrate. Pilot study

Abstract

The search for methods that identify early toxicity, induced by chemotherapy, is urgent. Changes in the biodistribution of radiopharmaceuticals could give information on early toxicity. Ten-week-old CD1 male mice were divided into four groups. Two groups were administered a weekly dose of 5 mg/kg of doxorubicin hydrochloride (DOX) for 5 weeks and the control groups were administered saline solution. One week after the end of treatment, the biodistribution of ¹⁸F-FDG and ⁶⁷Ga-citrate were carried out, as was the quantification of plasma enzymes CK, CK-MB, LDH and AST. All enzymes were higher in the treated animals, but only significant (p < 0.05) in the case of CK-MB. ¹⁸F-FDG uptake increased in all organs of treated animals except retroperitoneal fat, being significant in spleen, brain, heart, liver, lung, kidney, and inguinal fat. ⁶⁷Ga-citrate had a more complex pattern. The uptake in the DOX group was higher in spleen, lung, kidney, testes, and gonadal fat, it did not change in brain, heart, and liver, and it was lower in the rest of the organs. It only showed significant differences in lung and pancreas. A thorough discussion of the possible causes that produced the change in biodistributions of both radiopharmaceuticals is included. The pilot study showed that both radiopharmaceuticals could identify early multi-organ toxicity induced by DOX. Although ¹⁸F-FDG seems to be better, ⁶⁷Ga-citrato should not be ruled out a priori. The detection of early toxicity would serve to adopt treatments that prevent its progression, thus improving patient’s quality of life.

Keywords:

• Multi-organ toxicity
• doxorubicin
• ¹⁸F-FDG
• ⁶⁷Ga-citrate
• radiopharmaceuticals

Acknowledgments

The authors appreciate the graduate student scholarship granted to Julio César Córdoba-Adaya through the Programa Nacional de Posgrados de Calidad (PNPC; CONACyT). He is a graduate student from the M.Sc program in Medical Physics at UAEMex. Finally, the authors thank Dr. Eunice Olivé-Álvarez for her criticism, comments, and scientific discussions.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

The authors acknowledge the financial support received from the Universidad Autónoma del Estado de México (UAEMex), through grant 6257/2020CIB. This work was carried out as part of the activities of the Laboratorio Nacional de Investigación y Desarrollo de Radiofáramcos (LANIDER-CONACyT).