ABSTRACT
Objective:To observe the distribution of 177Lu-FA-DOTA-PEG-PLGA nanoparticles in vivo, and evaluate the therapeutic effect of nanoparticles intraperitoneal injection on ovarian cancer peritoneal metastases and ascites. Methods:Nanoparticles were prepared and injected into human ovarian cancer xenograft nude mice model by tail vein. Micro-SPECT/CT imaging was performed at different times (4, 24, 72 h and 7 d) after injection to observe the distribution of nanoparticles in vivo. Nude mouse models of intraperitoneal metastases of human ovarian cancer were randomly divided into negative control group (normal saline), chemotherapy group (cisplatin 3 mg/kg, twice a week) and nanoparticle group (18.5 MBq), with 4 mice in each group. After 7 days, intraperitoneal tumor growth was evaluated by in vivo fluorescence imaging. The relative tumor inhibition rate was counted. Tumor cell apoptosis rate was detected by TUNEL method, and the proliferation activity tumor Ki67 was detected by immunohistochemical method. The ascites volume of each group was compared after treatment. Results:Micro-SPECT/CT imaging showed the radioactive uptake of the transplanted tumor, and the 24 h tumor muscle uptake ratio (T/M) was the highest, about 2.81±0.49. Intravital fluorescence imaging showed that, after intraperitoneal administration, the fluorescence intensity of abdominal tumor in particle group, chemotherapy group and control group was (1.45±0.19)×10 10, (2.21±0.36)×10 10 and (2.63±0.79)×10 10( F=6.09, P=0.029), respectively. The relative tumor growth inhibition (TGI) of the particle group and the chemotherapy group were 35.6% and 18.6%, respectively. The tumor cell apoptosis rates in particle group and chemotherapy group were higher than those in control group ( F=9.96, P=0.009). Ki67 indexes in particle group and chemotherapy group were lower than those in control group ( F=9.93, P=0.013). The ascites volume in particle group and chemotherapy group were both smaller than those in control group ( F=13.43, P=0.006). Conclusions:177Lu-FA-DOTA-PEG-PLGA nanoparticles can be used for the targeted imaging of ovarian cancer. After intraperitoneal injection, nanoparticles show local retention, degradation and absorption and thus inhibit the growth of peritoneal metastases and ascites of ovarian cancer, which provides a new idea for the diagnosis and treatment of advanced ovarian cancer with peritoneal metastasis.
ABSTRACT
Radiotherapy forms one of the major treatment modalities for head and neck cancers (HNC), and precision radiotherapy techniques, such as intensity-modulated radiotherapy require accurate target delineation to ensure success of the treatment. Conventionally used imaging modalities, such as X-ray computed tomography (CT) and magnetic resonance imaging are used to delineate the tumor. Imaging, such as positron emission tomography (PET)-CT, which combines the functional and anatomic modalities, is increasingly being used in the management of HNC. Currently, 18-fluorodeoxyglucose is the most commonly used radioisotope, which is accumulated in areas of high glucose uptake, such as the tumor tissue. Because most disease recurrences are within the high-dose radiotherapy volume, defining a biological target volume for radiotherapy boost is an attractive approach to improve the results. There are many challenges in employing the PET-CT for radiotherapy planning, such as patient positioning, target edge definition, and use of new PET tracers, which represent various functional properties, such as hypoxia, protein synthesis, and proliferation. The role of PET-CT for radiotherapy planning is ever expanding and more clinical data underlining the advantages and challenges in this approach are emerging. In this article, we review the current clinical evidence for the application of functional imaging to radiotherapy planning and discuss some of the current challenges and possible solutions that have been suggested to date.