Hepato and Cardiotoxicity of Chemotherapeutic Treatment Evaluated by Means of Small Animal Imaging
Anti-cancer agents in medicinal chemistry(2017)
Abstract
Background: Chemotherapy is one of the most common approaches for cancer treatment. Particularly Doxorubicin has been proven to be effective in the treatment of many soft and solid tumors for locally advanced and metastatic cancer. It is not easy to clinically evaluate the chemotoxic or chemoprotective effect of some drugs, even more when there is a subclinical toxicity.Objective: To determine the usefulness of the hepatobiliary, colloid and cardiac scintigraphies, employing Tc-99m-disida, Tc-99m-phytate and Tc-99m-sestamibi respectively, in the evaluation of the hepato and cardiotoxicity of two chemotherapeutic treatments assessed in rats.Method: Two groups were submitted to doxorubicin (DOX) treatment and one was co-administered with histamine (DOX+HIS). Static Tc-99m-phytate and Tc-99m-sestamibi scintigraphies as well as a dynamic Tc-99m-disida study were performed in a small field of view gamma camera at: 0 weeks (control), 1 week and 2 weeks of treatment. Imagenological parameters were calculated: Liver/Bone Marrow ratio (L/BM), Heart/Background ratio (H/B) and time to the maximum (Tmax) for Tc-99m-phytate, Tc-99m-sestamibi and Tc-99m-disida extraction, respectively.Results: Control (L/BM=98 +/- 3; H/B=2.3 +/- 0.4; Tmax=8 +/- 3), DOX (L/BM: 85 +/- 3, 80 +/- 3; H/B, 3.5 +/- 0.5, 3.3 +/- 0.5 and Tmax 6 +/- 1, 4 +/- 1) for 1 and 2 weeks respectively and DOX+HIS (L/BM: 99 +/- 0.3, 98 +/- 1; H/B 2.9 +/- 0.5, 2.9 +/- 0.5 and Tmax, 8 +/- 2, 9 +/- 2) for 1 and 2 weeks, respectively. Histological analysis showed cardio and hepatotoxicity induced by doxorubicin.Conclusion: Imagenological parameters showed differences among treated and control groups and between both chemotherapy treatments. Thus, these radiopharmaceutical functional approaches were able to reflect heart and liver toxicity produced by doxorubicin.
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Key words
Doxorubicin,cardiotoxicity,hepatotoxicity,small animal imaging,Tc-99m-phytate,Tc-99m-disida,Tc-99m-sestamibi
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