Experimental study of 131I-caerin 1.1 and 131I-c(RGD)2 for internal radiation therapy of esophageal cancer xenografts.

OBJECTIVE: The aim of this study was to analyze and compare the therapeutic effects of 131I-caerin 1.1 and 131I-c(RGD)2 on TE-1 esophageal cancer cell xenografts. METHODS: (1) The in vitro antitumor effects of the polypeptides caerin 1.1 and c(RGD)2 were verified by MTT and clonogenic assays. 131I-caerin 1.1 and 131I-c(RGD)2 were prepared by chloramine-T (Ch-T) direct labeling, and their basic properties were measured. The binding and elution of 131I-caerin 1.1, 131I-c(RGD)2, and Na131I (control group) in esophageal cancer TE-1 cells were studied through cell binding and elution assays. (2) The antiproliferative effect and cytotoxicity of 131I-caerin 1.1, 131I-c(RGD)2, Na131I, caerin 1.1 and c(RGD)2 on TE-1 cells were detected by Cell Counting Kit-8 (CCK-8) assay. (3) A nude mouse esophageal cancer (TE-1) xenograft model was established to study and compare the efficacy of 131I-caerin 1.1 and 131I-c(RGD)2 in internal radiation therapy for esophageal cancer. RESULTS: (1) Caerin 1.1 inhibited the in vitro proliferation of TE-1 cells in a concentration-dependent manner, with an IC50 of 13.00 µg/mL. The polypeptide c(RGD)2 had no evident inhibitory effect on the in vitro proliferation of TE-1 cells. Therefore, the antiproliferative effects of caerin 1.1 and c(RGD)2 on esophageal cancer cells were significantly different (P < 0.05). The clonogenic assay showed that the clonal proliferation of TE-1 cells decreased as the concentration of caerin 1.1 increased. Compared with the control group (drug concentration of 0 µg/mL), the caerin 1.1 group showed significantly lower clonal proliferation of TE-1 cells (P < 0.05). (2) The CCK-8 assay showed that 131I-caerin 1.1 inhibited the in vitro proliferation of TE-1 cells, while 131I-c(RGD)2 had no evident inhibitory effect on proliferation. The two polypeptides showed significantly different antiproliferative effects on esophageal cancer cells at higher concentrations (P < 0.05). Cell binding and elution assays showed that 131I-caerin 1.1 stably bound to TE-1 cells. The cell binding rate of 131I-caerin 1.1 was 15.8 % ± 1.09 % at 24 h and 6.95 % ± 0.22 % after 24 h of incubation and elution. The cell binding rate of 131I-c(RGD)2 was 0.06 % ± 0.02 % at 24 h and 0.23 % ± 0.11 % after 24 h of incubation and elution. (3) In the in vivo experiment, 3 days after the last treatment, the tumor sizes of the phosphate-buffered saline (PBS) group, caerin 1.1 group, c(RGD)2 group, 131I group, 131I-caerin 1.1 group, and 131I-c(RGD)2 group were 68.29 ± 2.67 mm3, 61.78 ± 3.58 mm3, 56.67 ± 5.65 mm3, 58.88 ± 1.71 mm3, 14.40 ± 1.38 mm3, and 60.14 ± 0.47 mm3, respectively. Compared with the other treatment groups, the 131I-caerin 1.1 group had significantly smaller tumor sizes (P < 0.001). After treatment, the tumors were isolated and weighed. The tumor weights in the PBS group, caerin 1.1 group, c(RGD)2 group, 131I group, 131I-caerin 1.1 group, and 131I-c(RGD)2 group were 39.50 ± 9.54 mg, 38.25 ± 5.38 mg, 38.35 ± 9.53 mg, 28.25 ± 8.50 mg, 9.50 ± 4.43 mg, and 34.75 ± 8.06 mg, respectively. The tumor weights in the 131I-caerin 1.1 group were significantly lighter than those in the other groups (P < 0.01). CONCLUSION: 131I-caerin 1.1 has tumor-targeting properties, is capable of targeted binding to TE-1 esophageal cancer cells, can be stably retained in tumor cells, and has an evident cytotoxic killing effect, while 131I-c(RGD)2 has no evident cytotoxic effect. 131I-caerin 1.1 better suppressed tumor cell proliferation and tumor growth than pure caerin 1.1, 131I-c(RGD)2, and pure c(RGD)2.

131I-Caerin 1.1 and 131I-Caerin 1.9 for the treatment of non-small-cell lung cancer.

Objective: To investigate the effect of the 131I-labeled high-affinity peptides Caerin 1.1 and Caerin 1.9 for the treatment of A549 human NSCLC cells. Methods: ① 3-[4,5-Dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and plate clone formation assays were performed to confirm the in vitro anti-tumor activity of Caerin 1.1 and Caerin 1.9. ② Chloramine-T was used to label Caerin 1.1 and Caerin 1.9 with 131I, and the Cell Counting Kit 8 assay was performed to analyze the inhibitory effect of unlabeled Caerin 1.1, unlabeled Caerin 1.9, 131I-labeled Caerin 1.1, and 131I-labeled Caerin 1.9 on the proliferation of NSCLC cells. An A549 NSCLC nude mouse model was established to investigate the in vivo anti-tumor activity of unlabeled Caerin 1.1, unlabeled Caerin 1.9, 131I-labeled Caerin 1.1, and 131I-labeled Caerin 1.9. Results: ① Caerin 1.1 and Caerin 1.9 inhibited the proliferation of NSCLC cells in vitro in a concentration-dependent manner. The half-maximal inhibitory concentration was 16.26 µg/ml and 17.46 µg/ml, respectively, with no significant intergroup difference (P>0.05). ② 131I-labeled Caerin 1.1 and 131I-labeled Caerin 1.9 were equally effective and were superior to their unlabeled versions in their ability to inhibit the proliferation and growth of NSCLC cells (P>0.05). Conclusions: 131I-labeled Caerin 1.1 and 131I-labeled Caerin 1.9 inhibit the proliferation and growth of NSCLC cells and may become potential treatments for NSCLC.

Ectopic splenic autotransplantation following traumatic injury: A case report.

A 41-year-old male patient was admitted to the General Hospital of Guangzhou Military Command due to upper abdominal pain persisting for 12 h. Computed tomography (CT) and positron emission tomography/CT scans revealed multiple soft-tissue shadows in the abdominal cavity, peritoneum and Glisson's capsule, but the metabolic activity was at normal levels. A small area of low-density shadows near the tail of the pancreas and multiple shadows of enlarged lymph nodes were identified around the porta hepatis and the pancreas, with a mildly increased metabolic activity. On the basis of the CT images the patient was diagnosed with pancreatitis. Radionuclide imaging showed the absence of the spleen from its normal position (following splenectomy), but abnormal phagocytosis of multiple red blood cells was observed in the abdomen, which was diagnosed as ectopic splenic autotransplantation (ESAT). The patient subsequently recovered well following symptomatic treatment. ESAT in trauma patients requires urgent surgery in order to remove the damaged spleen and artificially cultivate partial splenic tissue.

[Diagnostic value of (18)F-FDG PET/CT for solitary nodular-type bronchoalveolar carcinoma].

OBJECTIVE: To assess the value of (18)F-FDG PET/CT in the diagnosis of solitary nodular-type bronchoalveolar carcinoma (BAC). METHODS: The clinical and radiographic data were analyzed retrospectively in 30 patients with pathologically confirmed solitary nodular-type BAC who underwent (18)F-FDG PET/CT examinations between August, 2005 and December, 2006. The morphological and radioactive findings of the lesions were reviewed, and the maximum standard uptake values (SUVmax) were measured. The diagnostic accuracy of PET, PET/CT, and HRCT were analyzed. RESULTS: The (18)F-FDG SUV was markedly lower in BAC than in other well differentiated adenocarcinoma. In 19 of the BAC cases, PET showed a SUVmax of no less than 2.5, demonstrating positive changes. Of the total of 30 cases, 5 had ground glass opacity (GGO) changes, 3 exhibited mixed nodules with GGO changes around the lesions, and 22 cases presented with solid nodules. HRCT showed that BAC located often in the superior lobes of the bilateral lungs, mostly below the pleura in the surrounding lung field; the lesions were patchy or nodular with irregular shapes, showing lobulation in 22 cases, spiculation in 15 cases, pleural indentation in 21 cases, and vacuolar changes in 4 cases. The diagnostic accuracy of PET, PET/CT and HRCT for solitary nodular-type BAC was 36.67%, 93.33%, and 93.33%, respectively. CONCLUSION: The SUVmax of BAC provides only limited value for defining the nature of the lesions, but can serve as a general reference for assessing the disease activity. PET/CT, which allows both functional and imaging assessment, can be a valuable modality to reduce the misdiagnosis rate of BAC.

[Diagnostic value of (18)F-FDG PET/CT for solitary nodular-type bronchoalveolar carcinoma].

OBJECTIVE: To assess the value of (18)F-FDG PET/CT in the diagnosis of solitary nodular-type bronchoalveolar carcinoma (BAC). METHODS: The clinical and radiographic data were analyzed retrospectively in 30 patients with pathologically confirmed solitary nodular-type BAC who underwent (18)F-FDG PET/CT examinations between August, 2005 and December, 2006. The morphological and radioactive findings of the lesions were reviewed, and the maximum standard uptake values (SUVmax) were measured. The diagnostic accuracy of PET, PET/CT, and HRCT were analyzed. RESULTS: The (18)F-FDG SUV was markedly lower in BAC than in other well differentiated adenocarcinoma. In 19 of the BAC cases, PET showed a SUVmax of no less than 2.5, demonstrating positive changes. Of the total of 30 cases, 5 had ground glass opacity (GGO) changes, 3 exhibited mixed nodules with GGO changes around the lesions, and 22 cases presented with solid nodules. HRCT showed that BAC located often in the superior lobes of the bilateral lungs, mostly below the pleura in the surrounding lung field; the lesions were patchy or nodular with irregular shapes, showing lobulation in 22 cases, spiculation in 15 cases, pleural indentation in 21 cases, and vacuolar changes in 4 cases. The diagnostic accuracy of PET, PET/CT and HRCT for solitary nodular-type BAC was 36.67%, 93.33%, and 93.33%, respectively. CONCLUSION: The SUVmax of BAC provides only limited value for defining the nature of the lesions, but can serve as a general reference for assessing the disease activity. PET/CT, which allows both functional and imaging assessment, can be a valuable modality to reduce the misdiagnosis rate of BAC.

PET/CT imaging of delayed radiation encephalopathy following radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: With the significant improvement in the survival of patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy and the growing availability of the sophisticated imaging modalities, the number of radiation encephalopathy (RE) cases relating to NPC radiotherapy is increasing. In this study, we investigated the metabolic and density changes of the compromised brain tissues during delayed RE using a positron-emission tomography-computed tomography (PET/CT) to provide clinical evidences for the diagnosis of delayed RE following radiotherapy for NPC. METHODS: The PET/CT manifestations and the clinical data of 53 pathologically confirmed NPC patients with delayed RE following radical radiotherapy and 15 healthy volunteers were investigated. The standardized uptake values (SUV) of the bilateral temporal lobes, the occipital lobe and the brain stem were measured respectively; and then the metabolic reduction rate of 88 temporal lobes and 13 brain stems were calculated for a statistical comparison between the two groups. RESULTS: The earliest case of delayed RE in the investigated patients occurred 1.5 years after radiotherapy. Delayed RE frequently involved the inferior temporal lobe. For patients with delayed RE confirmed by clinical symptoms and imaging findings, PET maintained a 100% coincidence rate with CT; however, in the 25 temporal lobes of the 35 delayed RE patients, PET revealed obvious hypometabolic changes whereas CT displayed normal density. The incidence of brain stem metabolic reductions was 24.5% (13/53) in the investigated patients, including 4 patients with hypometabolic changes shown by PET and negative finding shown by CT. The incidence of granuloma adjacent to the hypometabolic region in the temporal lobe was 12.5% (11/88). CONCLUSION: Delayed RE patients exhibit significant hypometabolic changes in the inferior temporal lobe, captured by PET much earlier than by CT. PET/CT offers a valuable means for the diagnosis of delayed RE in subacute stages and granuloma formation.

[Effects of lead acetate on expression of brain-derived neurotropic factor and P75NTR in rat brain].

OBJECTIVE: To study the effects of lead acetate on the expression of brain-derived neurotropic factor (BDNF) and its receptor P75NTR in rat brain. METHODS: Lead acetate was given to SD rats by intraperitoneal injection (ip) for 5 days at the dosage of 25, 50 and 100mg/kg body weight respectively. The contents of lead in serum, cerebral cortex and hippocampus were measured by atomic absorption spectrophotochemistry. The levels of BDNF mRNA and protein expression in cerebral cortex and hippocampus were observed by RT-PCR and immunohistochemistry, respectively. The levels of P75NTR protein expression in rat brain were measured by immunohistochemistry. RESULTS: Compared with the control, the contents of lead were significantly increased in serum, cerebral cortex and hippocampus in the treatment groups respectively (P < 0.01, P < 0.05). The BDNF mRNA expression in the cerebral cortex (0.52 +/- 0.05, 0.33 +/- 0.03) and hippocampus (0.77 +/- 0.10, 0.92 +/- 0.08) of 50, 100 mg/kg treated groups was significantly higher than that of the control group (0.52 +/- 0.05, 0.33 +/- 0.03), respectively (P < 0.05). The results of immunohistochemistry showed that the area density of BDNF protein in cerebral cortex of every treatment group (0.040 +/- 0.027, 0.048 +/- 0.027, 0.086 +/- 0.040) was significantly increased whereas the average gray value (187.11 +/- 11.15, 180.53 +/- 5.82, 180.15 +/- 8.01) was significantly lower than that of the control (0.026 +/- 0.005, 204.98 +/- 3.45) (P < 0.05, P < 0.01). The area density of BDNF protein in hippocampus of every treatment group was 0.040 +/- 0.027, 0.048 +/- 0.027, 0.086 +/- 0.040, respectively, which was significantly increased compared with the control (0.045 +/- 0.019, P < 0.05). The average gray value of BDNF protein in hippocampus (181.03 +/- 5.16, 171.25 +/- 12.65) of 50, 100 mg/kg were significantly lower than that of the control (198.98 +/- 6.40, P < 0.01). There was no positive expression of P75NTR protein in the control and 25 mg/kg body weight groups. The positive expression of P75NTR protein was detected in 50 and 100 mg/kg body weight groups. CONCLUSION: Lead can increase the BDNF and P75NTR expression in rat brain which might play an important role in the neural damage and repair.