Tumor vascular homing endgolin-targeted radioimmunotherapy in hepatocellular carcinoma.

Endoglin is a proliferation-associated cell membrane antigen and overexpressed in the angiogenic vasculature of solid tumors. However, the applications of endoglin (ENG)-targeted radioimmunotheray in hepatocellular carcinoma have not been reported yet. Therefore, the aim of this study was the visualization of both the development of hepatocellular carcinoma (HCC) tumor burden and therapeutic effect with ENG-targeted (131)I-anti-ENG mAb (A8), via in vivo noninvasive fluorescence imaging (NIFLI) of SMMC7721-green fluorescent protein (GFP) cells. A8 showed a dose-dependent, time-dependent suppression on the proliferation of SMMC7721-GFP cells and human umbilical vein endothelial cells (HUVECs) in vitro. Tube formation assay showed that (131)I-A8 markedly inhibits HUVECs to form extensive and enclosed tube networks. The results showed that the radiochemical purity of (131)I-A8 was 92.8 % and (131)I-A8 maintained more stable in serum than in saline and had high affinity against SMMC7721-GFP cells. The pharmacokinetics of (131)I-A8 was in accordance with the two-compartment model, with a rapid distribution phase and a slow decline phase. NIFLI exhibited a good relation between the fluorescent signal and tumor volume in vivo. Furthermore, treatment with (131)I-A8 resulted in significant tumor-growth suppression on the basis of the reducing fluorescent signal and a remarkably decreased tumor weight in treated animals. These results were further verified by RT-PCR and immunohistochemistry staining. Our findings indicate that (131)I-A8 can be used as ENG-targeted therapy for hepatocellular carcinoma, and noninvasive fluorescence imaging provides valuable information on tumor burden and effectiveness of therapy.

Radioiodine labeled anti-MIF McAb: a potential agent for inflammation imaging.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that may play a role in the pathogenesis of inflammation. Radiolabeled anti-MIF McAb can be used to detect in vivo inflammatory changes. The objective of this study was to investigate in vivo biology of radioiodinated anti-MIF McAb using the inflammation model mice. Anti-MIF McAb was radioiodinated with NaI125 by Iodogen method. Animal models were induced in the mice by intramuscular injection of S. aureus, E. coli, and turpentine oil. The biodistribution studies with radioiodinated anti-MIF McAb were performed on inflammation mice. The relationship between inflammatory lesions and anti-MIF McAb binding was investigated using the percent of injected dose per gram tissue (% ID/g) of tissue samples and whole-body autoradiography. The radioactivity of I125-anti-MIF McAb in the inflammatory tissue increased gradually for three inflammation models. The highest uptake was found in S. aureus group and the lowest was in E. coli group. The uptake in turpentine oil group was average. Whole-body autoradiography showed that all inflammation foci could be visualized clearly from 24 hours after injection, but 48 hours images were much clearer in accordance with the high T/NT ratio. These results demonstrate the ability of radioiodinated anti-MIF McAb to measure in vivo inflammatory events represented by high expression of MIF and suggests that radiolabeled anti-MIF McAb warrants further investigation as a potential inflammation-seeking agent for imaging to detect inflammatory disorders.

Effect of 131I 'clear residual thyroid tissue' after surgery on the function of parathyroid gland in differentiated thyroid cancer.

Thyroid cancer is a common malignant tumor of the endocrine glands. Although surgery is the optimal treatment utilized, the disease is characterized by recurrence and metastasis. The aim of the present study was to determine the effect of iodine-131 (131I) 'clear residual thyroid tissue' following surgery on the treatment of differentiated thyroid cancer (DTC) and its effect on the function of the parathyroid gland. A total of 160 patients diagnosed with DTC, who were consecutively admitted to our Hospital between June 2012 and June 2014 and underwent total thyroidectomy or subtotal resection, were included in the present study. After three months, the patients were administered 131I 'clear residual thyroid tissue' treatment and underwent a whole body scan after 1 week to determine whether 'clear residual thyroid tissue' treatment was successful or not. The treatment was repeated within 3 months if not successful. Of the 160 patients, 24 patients had cancer metastasis (15.0%). The average dose of 131I used for the first time was 6.4+1.2 GBq and the treatment was successful in 66 cases (41.3%). The average treatment time was 2.8±0.6 therapy sessions. The results showed that, prior to and following the first treatment and at the end of the follow up, levels of the parathyroid hormone, serum calcium and phosphorus were compared, and no statistically significant difference (P>0.05) was observed. There were 5 patients with persistent hypothyroidism and 8 patients with transient hypothyroidism. The levels of thyroglobulin were significantly decreased, and the difference was statistically significant (P<0.05). A total of 48 patients (30%) with hypothyroidism were identified. In conclusion, the results have shown that DTC resection and 131I 'clear residual thyroid tissue' treatment did not significantly impair the parathyroid function, thereby improving the treatment effect.

CT Perfusion Imaging Can Predict Patients' Survival and Early Response to Transarterial Chemo-Lipiodol Infusion for Liver Metastases from Colorectal Cancers.

OBJECTIVE: To prospectively evaluate the performance of computed tomography perfusion imaging (CTPI) in predicting the early response to transarterial chemo-lipiodol infusion (TACLI) and survival of patients with colorectal cancer liver metastases (CRLM). MATERIALS AND METHODS: Computed tomography perfusion imaging was performed before and 1 month after TACLI in 61 consecutive patients. Therapeutic response was evaluated on CT scans 1 month and 4 months after TACLI; the patients were classified as responders and non-responders based on 4-month CT scans after TACLI. The percentage change of CTPI parameters of target lesions were compared between responders and non-responders at 1 month after TACLI. The optimal parameter and cutoff value were determined. The patients were divided into 2 subgroups according to the cutoff value. The log-rank test was used to compare the survival rates of the 2 subgroups. RESULTS: Four-month images were obtained from 58 patients, of which 39.7% were responders and 60.3% were non-responders. The percentage change in hepatic arterial perfusion (HAP) 1 month after TACLI was the optimal predicting parameter (p = 0.003). The best cut-off value was -21.5% and patients who exhibited a ≥ 21.5% decrease in HAP had a significantly higher overall survival rate than those who exhibited a < 21.5% decrease (p < 0.001). CONCLUSION: Computed tomography perfusion imaging can predict the early response to TACLI and survival of patients with CRLM. The percentage change in HAP after TACLI with a cutoff value of -21.5% is the optimal predictor.

Imaging features of primary hepatic leiomyosarcoma: A case report and review of literature.

Primary hepatic leiomyosarcoma (PHL) is an extremely rare tumour. This tumour is difficult to diagnose by imaging examinations due to its rarity, and non-specific conventional imaging manifestations and clinical presentation. The present study reports the case of a 42-year-old male with PHL that was confirmed by histopathological and immunohistochemical examinations. Multimodal imaging examinations, including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT and digital subtraction angiography, were performed. The imaging manifestations were analysed and the associated literature was reviewed. The results found that no characteristic imaging appearance was present on ultrasound or plain CT scan. However, on unenhanced MRI, the tumours presented with a heterogeneous low signal density on T1-weighted imaging (WI) and a high signal density on T2WI and diffusion-WI. On gadopentetate dimeglumine enhanced MRI, the lesions were not enhanced during the arterial and portal venous phases; by contrast, these lesions were evidently enhanced during the 5-min delayed phase. Therefore, the delayed imaging of enhanced MRI is likely to be used to differentiate PHL from other hepatic tumours.

Imaging features of glucagonoma syndrome: A case report and review of the literature.

Glucagonoma syndrome appears as an extremely rare neuroendocrine tumour, with few studies ever having detailed its imaging manifestations. In particular, the magnetic resonance imaging (MRI) features of the lesion have not yet been reported. The present study describes a 54-year-old male who presented with uncontrollable skin erythema and weight loss that had been apparent for two years, and diabetes mellitus that had been apparent for five years. The glucagon level was 180 pg/ml. The plain abdominal computed tomography (CT) scan revealed a solid tumour in the neck of the pancreas, which was slightly reinforced during the arterial phase of the enhanced CT scan. Upon MRI, the lesion exhibited a low signal on T1-weighted imaging, and a slightly high signal on T2-weighted and half-Fourier acquisition single-shot turbo spin echo sequence imaging, which measured ~4.5×3.0×3.0 cm in size. Upon diffusion-weighted imaging, the lesion demonstrated heterogeneous hyperintensity, which was mildly enhanced during the arterial phase and washed out during the portal venous phase of gadopentetate dimeglumine-enhanced MRI. 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET)-CT identified a mild uptake of 18F-FDG by the lesion. The patient was diagnosed with glucagonoma syndrome, and a distal pancreatectomy and splenectomy were subsequently performed. Microscopy revealed that the tumour cells exhibited nest- and belt-like arrangements. The immunohistochemical staining identified positive reactions for glucagon, synaptophysin and chromogranin A, which are consistent with a diagnosis of glucagonoma. Following surgery, the symptoms disappeared and the glucagon level returned to normal. In conclusion, imaging examinations are useful for determining the location and size of a glucagonoma. In particular, MRI is able to identify the distinctive morphological features of the lesion. Immunohistochemical staining provides diagnostic evidence based upon the neuroendocrine features.

Role of 18F-FDG PET/CT in detecting pelvic lymph-node metastases in patients with early-stage uterine cervical cancer: comparison with MRI findings.

OBJECTIVE: This study aimed to investigate the applied value of F-fluoro-2-dexoxyglucose (F-FDG) PET/computed tomography (CT) and MRI in detecting lymph-node metastasis in early-stage cervical cancer. MATERIALS AND METHODS: A retrospective study was performed on 87 early-stage cervical cancer patients evaluated with PET/CT and pelvic MRI before surgery. Histopathological evaluation of lymph nodes served as the diagnostic standard. F-FDG PET/CT and MRI images were analyzed and correlated with histopathological findings. RESULTS: The overall node-based sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT were 91% (61/67), 78.2% (61/78), 99.4% (1079/1085), and 98% (1140/1163), respectively, which were higher than the corresponding values of MRI, at 37.3% (25/67), 61% (25/41), 96.3% (1080/1122), and 95% (1105/1163) (P<0.034). The difference in diagnostic efficacy for identifying node-based metastases between PET/CT and MRI was significant (PET/CT vs. MRI, 0.719 vs. 0.587, P=0.017). Meanwhile, the overall patient-based sensitivity, PPV, NPV, and accuracy of PET/CT were 100% (34/34), 87.2% (34/39), 100% (48/48), and 94.3% (82/87), respectively, whereas the corresponding MRI values were 44% (15/34), 65% (15/23),74% (45/61), and 69% (60/87) (P<0.04). The difference in diagnostic efficacy for identifying patient-based metastases between PET/CT and MRI was significant (PET/CT vs. MRI, 0.974 vs. 0.705, P<0.001). CONCLUSION: PET/CT has been proven to be valuable in detecting lymph-node metastases. Compared with MRI, PET/CT has higher sensitivity, PPV, NPV, and accuracy in patients with early-stage cervical cancer for detecting lymphatic metastases.

Thyroid tumor-initiating cells: increasing evidence and opportunities for anticancer therapy (review).

Accumulating evidence supports the notion that thyroid cancer is initiated by tumor-initiating cells (TICs) (commonly known as cancer stem cells), which are thought to play a crucial role in malignant progression, therapeutic resistance and recurrence. Thyroid TICs have been isolated and identified using specific biomarkers (such as CD133), the side population, sphere formation and aldehyde dehydrogenase activity assays. Although their characteristics remain largely unknown, TICs provide an attractive cellular mechanism to explain therapeutic refractoriness. Efforts are currently being directed toward the identification of therapeutic strategies that could target these cells. The present review discusses the cellular origins of TICs and the main approaches used to isolate and identify thyroid TICs, with a focus on the remaining challenges and opportunities for anticancer therapy.

Xanthogranulomatous osteomyelitis of rib mimicking malignant lesions in (18)F-FDG PET/CT imaging: a report of two cases.

Xanthogranulomatous osteomyelitis is a rare inflammatory process characterized histologically by collection of foamy macrophages admixed with mononuclear cells. We describe 2 cases with chest and back pain; radiography and CT scan identified expansile osteolytic rib destructive lesions with soft tissue mass. F-FDG PET/CT revealed accumulation of F-FDG similar to malignancy. Xanthogranulomatous osteomyelitis was histologically confirmed with numerous foamy histiocytes admixed with inflammatory infiltrate.

Evaluation of (131)I-anti-angiotensin II type 1 receptor monoclonal antibody as a reporter for hepatocellular carcinoma.

BACKGROUND: Finding a specific agent is useful for early detection of tumor. Angiotensin II type 1 receptor (AT1R) was reported to be elevated in a variety of tumors and participate in tumor progression. The aim of our study was to evaluate whether (131)I-anti-AT1R monoclonal antibody (mAb) is an efficient imaging reporter for the detection of hepatocellular carcinoma. METHODOLOGY/PRINCIPAL FINDINGS: AT1R mAb or isotype IgG was radioiodinated with (131)I and the radiochemical purity and stability of the two imaging agents and the affinity of (131)I-anti-AT1R mAb against AT1R were measured. 3.7 MBq (131)I-anti-AT1R mAb or isotype (131)I-IgG was intravenously injected to mice with hepatocellular carcinoma through tail vein, and then the whole-body autoradiography and biodistribution of the two imaging agents and the pharmacokinetics of (131)I-anti-AT1R mAb were studied. (131)I-anti-AT1R mAb and (131)I-IgG were successfully radioiodinated and both maintained more stable in serum than in saline. The (131)I-anti-AT1R mAb group showed much clearer whole-body images for observing hepatocellular carcinoma than the (131)I-IgG group. The biodistributions of the two imaging agents suggested that hepatocellular carcinoma tissue uptook more (131)I-anti-AT1R mAb than other tissues (%ID/g = 1.82±0.40 and T/NT ratio = 7.67±0.64 at 48 h), whereas hepatocellular carcinoma tissue did not selectively uptake (131)I-IgG (%ID/g = 0.42±0.06 and T/NT ratio = 1.33±0.08 at 48 h). The pharmacokinetics of (131)I-anti-AT1R mAb was in accordance with the two-compartment model, with a rapid distribution phase and a slow decline phase. These results were further verified by real-time RT-PCR, immunohistochemistry staining and Western blot. CONCLUSIONS/SIGNIFICANCE: (131)I-anti-AT1R mAb may be a potential target for early detection of tumor.

Positron emission tomography/computerized tomography in the evaluation of primary non-Hodgkin's lymphoma of prostate.

Primary malignant lymphoma of the prostate is exceedingly rare. Here we report a case of a 65-year-old man who presented with increased urinary frequency, urinary urgency, and urinary incontinence for two years. Benign prostatic hypertrophy was suspected at primary impression. Ultrasound revealed a hypoechoic lesion of the prostate. The total serum prostate-specific antigen was within normal range. Positron emission tomography/computerized tomography (PET/CT) showed a hypermetabolic prostatic lesion. Prostate biopsy was consistent with a non-germinal center diffuse large B cell lymphoma. There was complete remission of the prostatic lesion following six cycles of chemotherapy as shown on the second PET/CT imaging. ¹8F-fluoro-deoxy glucose PET/CT is not only a complement to conventional imaging, but also plays a significant role in the diagnosis and evaluation of treatment response of prostatic lymphoma.

Ascites metabolism measurement enhanced the diagnostic value and accuracy of prognostic evaluation in 18F-FDG PET/CT studies in malignant ascites patients.

OBJECTIVE: This study aimed to evaluate the role of ascites metabolism measurement in (18)F-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (CT) for auxiliary diagnosis and prognostic evaluation of malignant ascites. MATERIALS AND METHODS: This was a retrospective study on 55 patients, including 36 with malignant ascites and 19 with benign ascites of undetermined origin, before they underwent their first (18)F-FDG PET/CT scan. The χ(2) -test was used to compare the diagnostic efficiencies among (18)F-FDG PET/CT ascites metabolism measurement, tumor localization, and ascites cytology examination. The standard uptake values of ascites and of the normal liver were measured, respectively, and their ratio, denoted as T/NT, was calculated for each patient. The receiver-operating characteristic curve was used to analyze the diagnostic efficiency of the ascites T/NT, ascites carcinoembryonic antigen, ascites CA1(25), and ascites CA(199), and the linear regression was used to analyze the relationship between the ascites T/NT and the survival time of patients. RESULTS: The metabolic level of malignant ascites was high. The sensitivity and accuracy of ascites metabolism measurement were higher than those of ascites cytology examination (χ(2) =6.98, 4.58; all P's<0.05). The specificity of ascites metabolism measurement was higher than that of (18)F-FDG PET/CT tumor localization (χ(2) =5.70, P<0.05). The T/NT value of malignant ascites (0.68 ± 0.17) was higher than that of benign ascites (0.38 ± 0.10) (t=7.21, P<0.05). The area under the receiver-operating characteristic curve of ascites T/NT was larger than those of ascites carcinoembryonic antigen, CA(125), and CA(199). There was a negative correlation between the ascites T/NT and the survival of patients with malignant ascites (r=-0.647, P<0.01). CONCLUSION: Ascites metabolism measurement has an important auxiliary diagnostic value in (18)F-FDG PET/CT for ascites patients. The ascites T/NT may be a good index for prognostic evaluation of malignant ascites.

¹8F-fluorodeoxyglucose PET/CT findings of a solitary primary hepatic lymphoma: a case report.

Primary hepatic lymphoma is extremely rare, and only a few cases have been described on positron emission tomography (PET) or PET/computed tomography (PET/CT) imaging in the English literature. We report a case of a 55-year-old woman who presented with low-grade fever and weight loss of three months. On CT scanning, a mass was identified which appeared to be a hypoattenuating lesion, on ultrasonographic imaging, the mass was hypoechoic, therefore, liver abscess or hepatic metastasis from a gastrointestinal primary was initially suspected. Tumor markers such as alpha-fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19-9 were within normal limits. PET/CT demonstrated a large abnormal ring-like hypermetabolic focus in the right liver lobe. The lesion was resected and the histopathological findings were consistent with lymphoma. The patient was discharged two weeks after surgery and did not receive any further treatment. After 25 mo follow-up, she is in good health. (18)F-fluorodeoxyglucose PET/CT is useful in confirming the diagnosis of primary hepatic lymphoma by demonstrating no other foci with high uptake in other parts of the body.