Background Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of 188 Re-labeled nanoliposomes ( 188 Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated. Methods Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188 Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188 Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM ® computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188 Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared. Results In biodistribution, the highest uptake of 188 Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of 188 Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of 188 Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the 188 Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with 188 Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU). Conclusion The use of 188 Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that 188 Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.
Atypical slipped capital femoral epiphysis after radiotherapy and chemotherapy is uncommon. Only 32 cases have been reported in the literature. Because patients may have slippage at atypical ages, we report two cases of slipped capital femoral epiphysis in children and review the 32 cases previously reported to heighten clinicians' awareness of this condition in patients who have received radiation and chemotherapy for pelvic tumors. The controversy over prophylactic pinning of the uninvolved hip in radiotherapy-associated slipped capital femoral epiphysis is unresolved. It may be justifiable to fix the nonslipped epiphysis if possible prodromal signs of abnormal radiographic findings are detected. Because radiotherapy and chemotherapy were used in the two children reported, it is not possible to state whether one or both forms of treatment were responsible for the atypical slipped capital femoral epiphysis.
Liposomes can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness as well as reducing toxicity. To evaluate therapeutic strategies, it is essential to use animal models reflecting important safety aspects before clinical application. As our previous study found that a high dosage (185 of MBq) of (188) Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine-labeled pegylated liposomes ((188) Re-liposome) induced a decrease in white blood cell (WBC) count in Sprague-Dawley rats 7 days postinjection, the objective of the present study was to investigate extended acute radiotoxicity of (188) Re-liposome. Rats were administered via intravenous (i.v.) injection with (188) Re-liposome (185, 55.5 and 18.5 MBq), normal saline as a blank control or non-radioactive liposome as a vehicle control. Mortality, clinical signs, food consumption, body weights, urinary, biochemical and hematological analyzes were examined. In addition, gross necropsy and histopathological examinations were also performed at the end of the follow-up period. None of the rats died and no clinical sign was observed during the 28-day study period. Only male rats receiving (188) Re-liposome at a high dosage (185 MBq) displayed a slight weight loss compared with the control rats. In both male and female rats, the WBC counts of both high-dose and medium-dose (55.5 MBq) groups reduced significantly 7 days postinjection, but recovered to the normal range on Study Day 29. There was no significant difference in urinary analyzes, biochemical parameters and histopathological assessments between the (188) Re-liposome-treated and control groups. The information generated from the present study on extended acute toxicity of (188) Re-liposome will serve as a safety reference for radiopharmaceuticals in early-phase clinical trials.
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