Investigating the theragnostic potential of 131I-caerin peptide in thyroid cancer.

OBJECTIVE: Caerin is a new peptide with tumour toxicity and its uptake by tumour cells is independent of the sodium iodide symporter (NIS). Thyroid cancer is the most common cancers of endocrine malignancy. Radioiodine (131I)-refractory thyroid cancer is the most lethal subtype of the thyroid cancers and remains a clinical challenge. In the current study, we investigated the 131I radiolabeling efficiency of Caerin and the effects of Caerin, 131I-Caerin and free 131I on differentiated and undifferentiated human thyroid cancer cell lines (B-CPAP and CAL-62) in vitro. MATERIALS AND METHODS: Cell Counting Kit-8 was used to assess the cytotoxic effect of Caerin, 131I-Caerin and free 131I on B-CPAP and CAL-62 cells. Laser scanning confocal microscope was exploited to evaluate the uptake and internalization of Caerin by thyroid cancer cells. The Chloramine-T method was used to label the peptide with 131I. And the stability and water partition coefficient (Log P) of 131I-Caerin were studied. RESULTS: Our results demonstrated that Caerin and 131I-Caerin could be accumulated by B-CPAP and CAL-62 cells, resulting in killing of the thyroid cancer cells in vitro. The efficacy of 131I-Caerin is much higher than 131I, especially to undifferentiated CAL-62 cells. The results prove the feasibility of radioiodination of the 131I-Caerin via the Chloramine-T method. Moreover, the result indicate the hydrophobic 131I-Caerin was stable in 72 hours. CONCLUSION: Iodine-131-Caerin can inhibit the cell viability of thyroid cancer and hold certain promise as a theragnostic tool for human thyroid cancers.

Coronary arteriography in the diagnosis results and prognosis analysis of suspected coronary artery disease in patients with normal SPET myocardial perfusion imaging.

OBJECTIVE: Anatomic coronary artery disease (CAD) can be determined by coronary angiography (CAG) in patients with normal stress single photon emission tomography (SPET) myocardial perfusion imaging (MPI). Coronary angiography results of patients with negative exercise MPI and the prognosis of these patients (CAG-diagnosed CAD vs. non-CAD) were investigated in the current study. SUBJECTS AND METHODS: Suspected CAD patients who had SPET-MPI and subsequent CAG studies were retrospectively reviewed from May 2002 to November 2006. Siemens Diacam SPET and Siemens Ecam SPET γ-cameras were used for the examination of rest/exercise technetium-99m methoxy isobutyl isonitrile ((99m)Tc-MIBI) myocardial imaging. Coronary angiography was performed with Philips arura angiography machine by the standard Judkins method. RESULTS: In all, 6598 patients underwent clinically indicated rest/exercise (99m)Tc-MIBI SPET-MPI, and 133 patients underwent CAG despite negative MPI. Thirty one patients were diagnosed with CAD by CAG. Most of these lesions (66%) were located in distal vessels and most of these patients (68%) had 1 vessel disease. Age (P<0.01), hypertension (P<0.01), typical angina pectoris (P<0.01), high pretest likelihood of CAD (P<0.001), exercise induced angina (P<0.05), positive exercise ECG (P<0.01), and transient enlargement of scintigraphic left ventricular size (P<0.05) were significantly different between non-CAD and CAD groups. After median follow-up time of 53 ± 18 months, annualized cardiac event rate was 0.9% and 0.2% in CAD and non-CAD group, respectively (χ² = 1.22, P=0.27). CONCLUSION: In all, 23% of 133 patients in our study we confirmed anatomic CAD by CAG, despite negative findings in SPET-MPI. Several clinical, stress, and MPI findings could be potential predictors. However, similar to non-CAD group, the CAG diagnosed CAD patients negative (99m)Tc-MIBI SPET-MPI exercise test had a good prognosis with annualized cardiac event rate less than 1.0%.

Early monitoring of radiotherapeutic effects of nasopharyngeal carcinoma xenografts in nude mice using 18F-FDG PET-CT imaging.

BACKGROUND AND OBJECTIVE: Monitoring the therapeutic effects of radiotherapy for nasopharyngeal carcinoma (NPC) is critical to providing individualized treatment. This in-vivo study was initially designed to evaluate the therapeutic effect of radiotherapy using 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT) imaging. METHODS: 18F-FDG PET-CT imaging was performed on all of the 10 nude mice bearing NPC xenografts before radiotherapy, and early-phase and delayed-phase PET-CT images were performed on 7 of the 10 mice. All mice were randomly divided into either a control group or a radiotherapy group. The 5 mice in the control group were immediately killed after the imaging and pathology were performed. After receiving radiotherapy of 12 Gy, 5 animals in the radiotherapy group were given 18F-FDG PET-CT imaging on days 2, 4, and 6, and then were killed for pathologic evaluation. Regions of interest (ROI) technology was used to measure the tumor target/non-target (T/NT) ratio and the volume of the tumors. RESULTS: The average T/NT ratios of early- and delayed-phase imaging were 1.806 +/- 0.532 and 1.777 +/- 0.597, respectively, with no significance (P > 0.05). For the radiotherapy group, the average T/NT ratios for 18F-FDG PET-CT before radiotherapy, and on days 2, 4, and 6 after radiotherapy, were 1.735 +/- 0.466, 1.818 +/- 0.396, 1.096 +/- 0.101, and 0.604 +/- 0.108, respectively, The tumor volumes were (1.48 +/- 0.27) cm3, (1.57 +/- 0.31) cm3, (1.59 +/- 0.31) cm3 and (1.60 +/- 0.29) cm3, respectively. The average T/NT ratios of day 6 after radiotherapy and the other time points were significant (P < 0.05). The average death ratio of the tumor cells was (93.00 +/- 7.42)% after 6 days of post-radiotherapy. CONCLUSIONS: 18F-FDG PET-CT imaging can be used for the early assessment of radiotherapeutic effect of NPC in vivo. Day 6 after radiotherapy may be an appropriate time point for the imaging. However, the T/NT ratio measurement of delayed-phase imaging might make no sense for the diagnosis of NPC.

[Application of 99mTc-DTPA in evaluation of blood-brain barrier permeability in patients receiving whole brain irradiation].

OBJECTIVE: To study the pattern of blood-brain barrier (BBB) permeability changes during whole brain radiotherapy (WBRT) for metastatic brain tumor. METHODS: Twenty patients with metastatic brain tumors receiving WBRT by 6 MV X-ray underwent (99)mTc-DTPA brain SPECT before and during WBRT (20, 40 Gy) and at 2 weeks after the end of irradiation. A frame of transverse (99)mTc-DTPA brain SPECT image that best displayed the brain metastasis was chosen, and the regions of interest (ROI) were defined in the tumor foci (T), the contralateral normal brain tissue (N) and the background outside the soft tissues around the cranium (B). The radioactive counts of every ROI were measured and the ratios of the total counts (T/B and N/B) before and during WBRT (20 Gy, 40 Gy) and at 2 weeks after the irradiation were calculated. RESULTS: The average T/B and N/B in the 20 patients with 30 brain metastases was 142.2-/+51.1 and 82.6-/+42.3 before WBRT, 260.3-/+121.5 and 150.7-/+72.5 during 20 Gy WBRT, 251.6-/+118.3 and 161.8-/+68.4 during 40 Gy WBRT, and 250.3-/+117.2 and 158.6-/+73.5 at 2 weeks after the irradiation, respectively. The measurements during WBRT (20 and 40 Gy) and at 2 weeks after the irradiation group underwent no significant variations (P>0.05), but showed significant differences from those before WBRT (P<0.05). CONCLUSIONS: Irradiation causes direct damage of the BBB function, and the permeability of the BBB increases significantly during and within 2 weeks following 20 and 40 Gy WBRT, which provides the optimal time window for interventions with chemotherapy.

[Standard uptake value of 18F-fluorine-2-deoxyglucose is correlated with the expression of estrogen receptor in duct carcinoma of breast].

OBJECTIVE: To explore the relationship between the standard uptake value (SUV) of 18F-fluorine-2-deoxyglucose (18F-FDG) and the expression of estrogen receptor (ER) in duct carcinoma of breast, as well as their correlation. METHODS: From March 2004 to November 2006, PET/CT scans were performed to 41 patients (female, mean age (55.2 +/- 9.55) years) with duct carcinoma of breast. All of the diagnoses were proved by pathology and immunohistochemical ER assays. The SUVs were calculated. RESULTS: ER positive patients comprised 43.9% of the 41 patients. The mean age of ER positive patients was (60.20 +/- 9.34) years, older than the ER negative patients ((50.32 +/- 9.33) years, P = 0.012). The SUV in the ER positive patients (2.76 +/- 1.34) was significantly less than in the ER negative patients (5.84 +/- 2.90, P = 0 004). The receiver operating characteristic (ROC) by FDG SUV for ER demonstrated that the area under curves reached 0.801 +/- 0.075, with significant implications on the expression of estrogen receptor (P = 0.002); The cut point of FDG SUV for ER was 3.135, with sensitivity of 72.2% and specificity of 73.9%. CONCLUSION: 18F-FDG SUV is significantly correlated with the expression of ER. We propose 3.135 as a threshold of SUV for the indication of expression of ER in duct carcinoma of breast.

Tissue specific expression of suicide genes delivered by nanoparticles inhibits gastric carcinoma growth.

Developing an efficient and safe strategy to introduce a therapeutic gene into targeting cells in vivo is a key issue in cancer gene therapy nowadays. Novel non-viral gene carriers, such as nanoparticles, have been shown to be able to deliver DNA into cancer cells efficiently. Suicide gene therapy has been demonstrated to be effective in inhibiting tumor growth, however, the lack of tumor specificity limits its application in clinic. Developing a targeting system for suicide gene is an attractive strategy in cancer gene therapy. In this study, the CMV enhancer and carcinoembryonic antigen (CEA) promoter was fused to a chimeric suicide gene yCDglyTK. This construct was delivered into SGC7901 gastric cancer cells using calcium phosphate nanoparticles (CPNPs). The expression of yCDglyTK in SGC7901 cells was confirmed by RT-PCR and western blot. Immunofluorescence experiments showed that yCDglyTK is only expressed in CEA-positive cancer cells, but not in CEA-negative cells. The expression of yCDglyTK induced cancer cell death following the addition of the prodrug 5-FC, and also elicit "bystander effect" to kill the neighboring cells. Intratumoral injection of CPNP-yCDglyTK complex followed by administration of 5-FC produced marked regression in gastric cancer xenografts. Taken together, our study suggests that the combination of calcium phosphate nanoparticles and suicide gene therapy represents a novel approach for targeting gastric cancer gene therapy.

Characterization and application of monoclonal antibodies against N protein of SARS-coronavirus.

Severe acute respiratory syndrome-coronavirus (SARS-CoV) causes an infectious disease through respiratory route. Diagnosing the disease effectively and accurately at early stage is essential for preventing the disease transmission and performing antiviral treatment. In this study, we raised monoclonal antibodies (mAbs) against the nucleocapsid (N) protein of SARS-CoV and mapped epitopes by using different truncated N protein fragments. The mapping of those epitopes was valuable for constructing pair-Abs used in serological diagnosis. The results showed that all of the six raised mAbs were divided into two groups recognizing the region of amino acids 249-317 (A group) or 317-395 (B group). This region spanning amino acids 249-395 contains predominant B cell epitopes located at the C-terminus of N protein. One pair-Abs, consisting of N protein-specific rabbit polyclonal antibody and SARS-CoV N protein-specific mAb, was selected to construct a sandwich ELISA-kit. The kit was able to specifically detect SARS-CoV N proteins in serum samples.