Preliminary evaluation of acute toxicity of 188Re-BMEDA-liposome in rats
| Autor: | Tung-Chuan Chiang, Chih-Hsien Chang, Ya-Jen Chang, Liang-Cheng Chen, Hsiao-Lin Chen, Chin-Wei Hsu, Chi-Mou Liu, Chia-Yu Yu, Tsui-Jung Chang, Chung-Li Ho, Te-Wei Lee |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Pathology medicine.medical_specialty medicine.medical_treatment Drug Evaluation Preclinical Pharmacology Toxicology Polyethylene Glycols Rats Sprague-Dawley Random Allocation Weight loss White blood cell Organometallic Compounds Toxicity Tests Acute Animals Medicine Saline Chelating Agents Liposome business.industry Cancer Ethylenediamines medicine.disease Acute toxicity Rats Clinical trial Rhenium medicine.anatomical_structure Injections Intravenous Liposomes Toxicity Female medicine.symptom business |
| Zdroj: | Journal of Applied Toxicology. 30:680-687 |
| ISSN: | 0260-437X |
| DOI: | 10.1002/jat.1541 |
| Popis: | Liposomes can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. To evaluate therapeutic strategies, it is essential to use animal models reflecting important safety aspects before clinical application. The objective of this study was to investigate acute radiotoxicity of 188Re-N,N-bis (2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA)-labeled pegylated liposomes (188Re–BMEDA–liposome) in Sprague–Dawley rats. Rats were administered with 188Re–BMEDA–liposome, normal saline as blank or non-radioactive liposome as vehicle control via intravenous injection and observed for 14 days. Examinations were conducted with respect to mortality, clinical signs, food consumption, body weight and hematological and biochemical analyses. In addition, gross necropsy, histopathological examinations and cytogenetic analyses were also performed. None of the rats died and no clinical sign was observed during the 14-day study period. Rats administered with 188Re–BMEDA–liposome at dosage of 185 MBq displayed a significant weight loss compared with the control from study day (SD) 1 to SD 4, and the white blood cell count reduced to 5–10% of initial value (female: 18.55 ± 6.58 to 0.73 ± 0.26 × 103 µl−1; male: 14.52 ± 5.12 to 1.43 ± 0.54 × 103 µl−1) 7 days-post injection, but were found to have recovered on SD 15. There were no significant differences in biochemical parameters and histopathological assessments between the 188Re–BMEDA–liposome-treated and control groups. The frequencies of dicentric chromosomes were associated with dosage of 188Re–BMEDA–liposome. The information generated from this study on acute toxicity will serve as a safety reference for further subacute toxicity study in rats and human clinical trials. Copyright © 2010 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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