Hepato and Cardiotoxicity of Chemotherapeutic Treatment Evaluated by Means of Small Animal Imaging.

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, employing99mTcdisida, 99mTc-phytate and 99mTc-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 99mTc-phytate and 99mTc-sestamibi scintigraphies as well as a dynamic 99mTc-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 99mTc-phytate, 99mTc-sestamibi and 99mTc-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.

Radiolabeling and biological characterization of TPGS-based nanomicelles by means of small animal imaging.

INTRODUCTION: In recent years, nanomedicines have raised as a powerful tool to improve prevention, diagnosis and treatment of different pathologies. Among the most well investigated biomaterials, D-α-tocopheryl polyethylene glycol succinate (also known as TPGS) has been on the spot for the last decade. We therefore designed a method to biologically characterize TPGS-based nanomicelles by labeling them with 99mTc. METHODS: Labeling process was performed by a direct method. The average hydrodynamic diameter of TPGS nanomicelles was measured by dynamic light scattering and radiochemical purity was assessed by thin layer chromatography. Imaging: a dynamic study was performed during the first hour post radioactive micelles administration in a gamma camera (TcO4- was also administered for comparative purposes). Then two static images were acquired in ventral position: 1h and 12h post injection. Blood pharmacokinetics of 99mTc-TPGS during 24h was performed. RESULTS: Images revealed whole body biodistribution at an early and delayed time and semiquantification was performed in organs of interest (%Total counts: soft tissue 6.1±0.5; 3.9±0.1, Bone 1.2±0.2; 1±0.1, Heart 1.5±0.6; 0.7±0.3, Kidneys 16.6±1.3; 26.5±1.7, Liver 8.6±1.1; 11.1±0.1 for 1 and 12 h post injection respectively). CONCLUSION: This work demonstrated that TPGS based nanomicelles are susceptible to be radiolabeled with 99mTc thus they can be used to perform imaging studies in animal models. Moreover radiolabeling of these delivery nano systems reveals their possibility to be used as diagnostic agents in the near future.