Single-Fraction Palliative High-Dose-Rate Brachytherapy for Symptom Management in a 97-Year-Old Patient With Dementia.

Background: Delivering cancer treatment to elderly patients with dementia is often challenging. We describe performing palliative surface mold brachytherapy (SMBT) in an elderly patient with advanced dementia for pain control using music therapy to assist with agitation. Case Description: The patient was a 97-year-old Japanese woman with advanced dementia. Exudate was observed from her tumor, and she complained of Grade 2 severity pain using Support team assessment schedule (STAS), especially when undergoing would dressings. Given her advanced dementia, she was not considered a candidate for radical surgery or external beam radiotherapy. We instead treated her with high-dose-rate (HDR) SMBT. Due to her advanced dementia associated with agitation, she could not maintain her position. She was able to remain calm while listening to traditional Japanese enka music, which enables our team to complete her radiation without using anesthetics or sedating analgesics. Her localized pain severity decreased ≤21 days and the exudate fluid disappeared ≤63 days after HDR-SMBT. Her tumor was locally controlled until her death from intercurrent disease 1 year after HDR-SMBT. Discussion: Single fraction palliative HDR-SMBT was useful for successful treatment of skin cancer in an elderly patient. Traditional Japanese music helped reduce her agitation to complete HDR-SMBT. For elderly patients with agitation associated with dementia, we should consider using music and music therapy to facilitate radiation therapy.

HDR-brachytherapy for accelerated partial breast irradiation: Long-term experience from a Japanese institution.

Purpose: We investigated the long-term oncological outcome of high-dose-rate (HDR) multicatheter interstitial brachytherapy (MIB) for adjuvant accelerated partial breast irradiation (APBI) after breast conserving surgery in Japanese patients. Material and methods: Between June 2002 and October 2011, 86 breast cancer patients were treated at National Hospital Organization Osaka National Hospital (trial number of the local institutional review board, 0329). Median age was 48 years (range, 26-73 years). Eighty patients had invasive and 6 patients non-invasive ductal carcinoma. Tumor stage distribution was pT0 in 2, pTis in 6, pT1 in 55, pT2 in 22, and pT3 in one patient, respectively. Twenty-seven patients had close/positive resection margins. Total physical HDR dose was 36-42 Gy in 6-7 fractions. Results: At a median follow-up of 119 months (range, 13-189 months), the 10-year local control (LC) and overall survival rate was 93% and 88%, respectively. Concerning the 2009 Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology risk stratification scheme, the 10-year LC rate was 100%, 100%, and 91% for patients considered as low-risk, intermediate-risk, and high-risk, respectively. According to the 2018 American Brachytherapy Society risk stratification scheme, the 10-year LC rate was 100% and 90% for patients 'acceptable' and 'unacceptable' for APBI, respectively. Wound complications were observed in 7 patients (8%). Risk factors for wound complications were the omission of prophylactic antibiotics during MIB, open cavity implantation, and V100 ≥ 190 cc. No grade ≥ 3 late complications (CTCVE version 4.0) were observed. Conclusions: Adjuvant APBI using MIB is associated with favorable long-term oncological outcomes in Japanese patients for low-risk, intermediate-risk, and acceptable groups of patients.

Carcinoma of Unknown Original Identified as Renal Cell Carcinoma by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scan: A Report of Two Cases.

Imaging is useful in identifying the primary site of an unknown primary cancer, and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is an excellent imaging modality for identifying the primary lesion. However, a potential limitation is that 18F-FDG is physiologically excreted from the kidneys, thus masking renal lesions. In this report, we describe two cases of cancer of unknown origin that were detected as originating from renal cancer on 18F-FDG PET/CT. Both cases showed abnormal nodular accumulation of 18F-FDG in the kidney, which can be distinguished from the physiological excretion of 18F-FDG in the urinary tract. It is clinically crucial to be able to confirm the possibility of renal cancer, and careful observation of the urinary tract with 18F-FDG PET/CT can be useful.

Practical Radiation Protection for Interventional Radiologist.

As per the International Commission on Radiological Protection 2010 recommendation, it was stated that "interventional radiologists performing difficult procedures with high workloads may be exposed to high doses" and that education and training of medical staffs in radiation exposure is "an urgent priority." There are many reports on the textbook aspects of radiation protection, but reports on the practical aspects of radiation protection have remained to be scarce. Various methods of reducing radiation exposure are described as "useful" or "can be reduced," but the priority of these methods and the "extent" to which they contribute to reducing radiation exposure are not clear. Thus, in this article, we will look into the protection of interventional radiologist from radiation exposure in a practical way, giving priority to clarity rather than academic accuracy.

Efficacy of Combination Therapy with Lenvatinib and Radioactive Iodine in Thyroid Cancer Preclinical Model.

Patients with differentiated thyroid cancer (DTC) usually have good prognosis, while those with advanced disease have poor clinical outcomes. This study aimed to investigate the antitumor effects of combination therapy with lenvatinib and 131I (CTLI) using three different types of DTC cell lines with different profiling of sodium iodide symporter (NIS) status. The radioiodine accumulation study revealed a significantly increased radioiodine uptake in K1-NIS cells after lenvatinib treatment, while there was almost no uptake in K1 and FTC-133 cells. However, lenvatinib administration before radioiodine treatment decreased radioiodine uptake of K1-NIS xenograft tumor in the in vivo imaging study. CTLI synergistically inhibited colony formation and DTC cell migration, especially in K1-NIS cells. Finally, 131I treatment followed by lenvatinib administration significantly inhibited tumor growth of the NIS-expressing thyroid cancer xenograft model. These results provide important clinical implications for the combined therapy that lenvatinib should be administered after 131I treatment to maximize the treatment efficacy. Our synergistic treatment effects by CTLI suggested its effectiveness for RAI-avid thyroid cancer, which retains NIS function. This potential combination therapy suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer.

A comparison of HER2/neu accumulations of Ga-67-labeled anti-HER2 antibody with chemically and site-specifically conjugated bifunctional chelators.

Monoclonal antibodies (mAb) developed to target specific cancers have achieved considerable success to date. To further enhance therapeutic efficacy, monoclonal antibodies may be conjugated with a cytotoxic drug or radioisotope. We present the development of a new method based on site-specific conjugation (SSC) for targeting HER2. The study design involves a comparison of the accumulation of Ga-67-labeled anti-HER2 antibodies with SSC (SSC-mAb) versus conventional chemical conjugation (Chem-mAb) in HER2-positive tumors. In vitro, the HER2-binding capacity of SSC-mAb and Chem-mAb was comparable. However, in vitro, the rate of tumor accumulation increased gradually with SSC-mAb not only in the tumors but also in the blood and other organs. The SSC may improve targeted antigen-specific cancer radioimmunotherapy and may, due to higher retention, reduce the amount of treatment required.

Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor.

Although surgical treatment cures >90% of differentiated thyroid cancer (DTC) patients, the remaining patients, including advanced DTC cases, have poor clinical outcomes. These patients with inoperable disease have only two choices of radioactive iodine therapy and tyrosine kinase inhibitors such as lenvatinib, which have a high incidence of treatment-related adverse events and can only prolong progression free survival by approximately 5-15 months. In this study, we investigated the antitumor effects of combination therapy with lenvatinib and radiation (CTLR) for DTC. CTLR synergistically inhibited cell replication and colony formation in vitro and tumor growth in nude mice without apparent toxicities and suppressed the expression of proliferation marker (Ki-67). CTLR also induced apoptosis and G2/M phase cell cycle arrest. Moreover, quantitative analysis of the intracellular uptake of lenvatinib using liquid chromatography and mass spectrometry demonstrated that intracellular uptake of lenvatinib was significantly increased 48 h following irradiation. These data suggest that increased membrane permeability caused by irradiation increases the intracellular concentration of levatinib, contributing to the synergistic effect. This mechanism-based potential of combination therapy suggests a powerful new therapeutic strategy for advanced thyroid cancer with fewer side effects and might be a milestone for developing a regimen in clinical practice.

A Novel Approach for Investigating Upper Airway Hyperresponsiveness Using Micro-CT in Eosinophilic Upper Airway Inflammation such as Allergic Rhinitis Model.

Airway hyperresponsiveness (AHR) has been proposed as a feature of pathogenesis of eosinophilic upper airway inflammation such as allergic rhinitis (AR). The measurement system for upper AHR (UAHR) in rodents is poorly developed, although measurements of nasal resistance have been reported. Here we assessed UAHR by direct measurement of swelling of the nasal mucosa induced by intranasal methacholine (MCh) using micro-computed tomography (micro-CT). Micro-CT analysis was performed in both naïve and ovalbumin-induced AR mice following intranasal administration of MCh. The nasal cavity was segmented into two-dimensional horizontal and axial planes, and the data for nasal mucosa were acquired for the region of interest threshold. Then, a ratio between the nasal mucosa area and nasal cavity area was calculated as nasal mucosa index. Using our novel method, nasal cavity structure was clearly identified on micro-CT, and dose-dependent increased swelling of the nasal mucosa was observed upon MCh treatment. Moreover, the nasal mucosa index was significantly increased in AR mice compared to controls following MCh treatment, while ovalbumin administration did not affect swelling of the nasal mucosa in either group. This UAHR following MCh treatment was completely reversed by pretreatment with glucocorticoids. This novel approach using micro-CT for investigating UAHR reflects a precise assessment system for swelling of the nasal mucosa following MCh treatment; it not only sheds light on the mechanism of AR but also contributes to the development of new therapeutic drugs in AR patients.

[Improvement in Hyperglysemia Following Unilateral Adrenalectomy for ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH) : A Case Report].

Adrenal corticotropin (ACTH) -independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome. Bilateral adrenalectomy is the treatment of choice, but lifetime steroid replacement is essential. Here we report a case of AIMAH whose hyperglycemia was improved following unilateral adrenalectomy. A 42-year-old woman with serious intellectual disability and intractable epilepsy presented with polydipsia. Casual blood glucose and hemoglobin A1c (HbA1c) were 322 mg/dl and 8.5%, respectively. The cortisol level was high and ACTH level was low. Abdominal computed tomography and magnetic resonance imaging revealed unsuspected macronodular enlargement of bilateral adrenal glands (left 8 cm, right 4 cm in maximal diameter) and she was diagnosed with AIMAH. Both adrenal glands showed intense 131 I-adosterol accumulation predominantly in the left side and left-unilateral laparoscopic adrenalectomy was performed. Both insulin and oral antidiabetic drugs could be cancelled postoperatively, and HbA1c decreased to 5.7%. Steroid was not replaced but she never experienced adrenal crisis. We conclude that unilateral adrenalectomy is a safe and effective treatment for certain cases of AIMAH.

Discovering EEG resting state alterations of semantic dementia.

OBJECTIVE: Diagnosis of semantic dementia relies on cost-intensive MRI or PET, although resting EEG markers of other dementias have been reported. Yet the view still holds that resting EEG in patients with semantic dementia is normal. However, studies using increasingly sophisticated EEG analysis methods have demonstrated that slightest alterations of functional brain states can be detected. METHODS: We analyzed the common four resting EEG microstates (A, B, C, and D) of 8 patients with semantic dementia in comparison with 8 healthy controls and 8 patients with Alzheimer's disease. RESULTS: Topographical differences between the groups were found in microstate classes B and C, while microstate classes A and D were comparable. The data showed that the semantic dementia group had a peculiar microstate E, but the commonly found microstate C was lacking. Furthermore, the presence of microstate E was significantly correlated with lower MMSE and language scores. CONCLUSION: Alterations in resting EEG can be found in semantic dementia. Topographical shifts in microstate C might be related to semantic memory deficits. SIGNIFICANCE: This is the first study that discovered resting state EEG abnormality in semantic dementia. The notion that resting EEG in this dementia subtype is normal has to be revised.

Neuropsychological Evaluation and Cerebral Blood Flow Effects of Apolipoprotein E4 in Alzheimer's Disease Patients after One Year of Treatment: An Exploratory Study.

BACKGROUND: Alzheimer's disease (AD) is affected by apolipoprotein E (ApoE); however, its effects assessed by means of cognitive tests and by neuroimaging have not been sufficiently studied. METHODS: We administered the Alzheimer's Disease Assessment Scale (ADAS) and single-photon emission computed tomography imaging in patients with AD medicated with donepezil at baseline and after 1 year. Patients were classified as with or without ApoE4 and we evaluated the progress of AD. RESULTS: Analysis of covariance showed that cerebral blood flow after 1 year in subjects with ApoE4 is significantly reduced in some areas including the left lenticular nucleus, left thalamus, and right hippocampus compared with subjects without ApoE4. Paired t tests showed significantly reduced blood flow in several regions including the right hippocampus in subjects with ApoE4 and significant deterioration of ideational praxis in subjects without ApoE4. CONCLUSION: This study provides evidence that supports the notion of ApoE4 playing an important role in the progress of AD.

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis].

BACKGROUND: Dexmedetomidine (Precedex®)is an agonist of a2-adrenergic receptors in certain parts of the brain. It was approved for "procedural sedation in the non-intubation in under local anesthesia" in June 2013 in Japan. However, because of metabolism delay, dexmedetomidine has to be administered carefully to patients with liver dysfunction. PURPOSE: To evaluate the feasibility and safety of sedation using dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction. METHODS: Thirty consecutive cases of percutaneous arterial chemoembolization for hepatocellular carcinoma with hepatitis C-related cirrhosis(male, 23; female, 7; age, 74±5.9; weight, 62.7±12.3 kg; Child-Pugh A, 23; Child-Pugh B, 7)were analyzed retrospectively. Dexmedetomidine was administered at 3 mg/kg/h for 15 minutes as the initial loading dose and at 0.4 mg/kg/h as the maintenance dose. The sedation level was evaluated using the Ramsay sedation scale. RESULTS: In 30 of 30 cases, percutaneous arterial chemoembolization therapy could be performed with dexme- detomidine sedation. In 27 of 30 cases, the procedure was completed with the maintenance dose of 0.4 mg/kg/h. In 3 of 30 cases, the maintenance dose was increased to 0.6 mg/kg/h because of patient body motion. The mean administration time of dexmedetomidine was 82±30 minutes. The level of sedation measured with the Ramsay sedation scale at the end of the procedure was 3 points in 29 cases and 5 points in one case. Adverse events occurred in 3 of 30 cases. Intravenous drip leakage occurred in one case, vertigo occurred in one case, and vomiting occurred in one case. There were no adverse events requiring treatment. CONCLUSION: Sedation with dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction was feasible and safe.

The effect of radiation exposure on multidrug resistance: in vitro and in vivo studies using non-small lung cancer cells.

BACKGROUND: Technetium-99m methoxyisobutylisonitrile (Tc MIBI) is a substrate with the same uptake kinetics as doxorubicin. Multidrug resistance (MDR) is a mechanism that impedes chemotherapy of non-small cell lung cancer (NSCLC). We examined the effect of radiation exposure on MDR in NSCLC and the synergy between an MDR modulator, GG918, and radiation, using (99m)Tc MIBI in vitro and doxorubicin in vivo. METHODS: In vitro NSCLC cells (H1299) were exposed to radiation (3-, 6-, and 9-Gy-irradiated groups) alongside a not-irradiated (0 Gy) group. Technetium-99 metastable methoxyisobutylisonitrile ((99m)Tc MIBI) was administered to cell suspensions at 48 h after irradiation. Cell radioactivity was measured, and C in/C out ratios were calculated and compared. NSCLC cells were also subcutaneously transplanted into the left thigh of nude mice, which were subsequently raised for 2 weeks. Two groups of mice were used: mice exposed to irradiation (9-Gy-irradiated) and those that were not (not-irradiated). Doxorubicin was administered through the caudal vein at 48 h after the irradiation. Using an in vivo imaging system, intratumoural photon counts were measured. To determine the synergy between the MDR modulator and 3- or 6-Gy irradiation, the final GG918 concentration was determined: 0.1 µM (N-H, 3-H, and 6-H groups), 0.001 µM (N-L, 3-L, and 6-L groups), and 0 µM (N-0, 3-0, and 6-0 groups). C in/C out ratios were calculated and compared among the groups. RESULTS: C in/C out after 6- or 9-Gy irradiation was significantly higher than that of the not-irradiated group (0 Gy). In vivo, fluorescence photon counts were significantly higher in the tumours of 9-Gy-irradiated mice, up to 270 min after administration of doxorubicin, as compared to the not-irradiated mice. The C in/C out ratio in the N-H, 3-H, and 6-H groups was significantly higher than that in the N-0, 3-0, and 6-0 groups. There was no significant difference between C in/C out in the N-L group and that of the N-0 group. However, the C in/C out ratio in the 3-L and 6-L groups was significantly higher than that in the 3-0 and 6-0 groups. CONCLUSIONS: Irradiation decreased MDR in NSCLC cells. In combination with a low-dose MDR modulator, GG918, MDR transport function was synergistically reduced 48 h post-irradiation.

Longitudinal time-dependent effects of irradiation on multidrug resistance in a non-small lung cancer cell line.

Multidrug resistance (MDR) in cancer is known to decrease the therapeutic efficacy of chemotherapy. The effects of irradiation on MDR in cancer cells remain unclear. Tc-99m methoxyisobutylisonitrile (MIBI) exhibits the same ATP-binding cassette (ABC) transporter kinetics as the chemotherapeutic compound doxorubicin. In this study, we investigated the synergistic effects of chemotherapeutics and irradiation [0 Gy: C (control) group; 3, 6, 9, 12 Gy: I (irradiation) group] in the human non-small lung cancer cell line H1299 exhibiting MDR, on MIBI and doxorubicin ABC transporter kinetics, in vitro and in vivo, respectively. In vitro, inhibition of H1299 cell proliferation by irradiation was found to be irradiation dose dependent. The degree and duration of MDR inhibition in vitro in H1299 were also dose dependent. In the cells of both the C group and 3-Gy I group, no significant difference of MIBI accumulation was observed. In the 6-Gy I group, a higher MIBI accumulation was observed at only 7 days after irradiation relative to the C group. A higher MIBI accumulation in the 9- and 12-Gy I groups with a significant difference from the C group was observed at 4 to 14 days after irradiation. A significant negative correlation between intracellular MIBI accumulation and cell replication was found. In vivo, high accumulation and retention of doxorubicin were observed in irradiated tumors in the H1299 xenograft mice group at 4 to 14 days after 9-Gy irradiation compared with the control mice group. These results provide evidence for a synergistic effect of concurrent chemotherapy and radiotherapy.

Radiation dose of nurses during IR procedures: a controlled trial evaluating operator alerts before nursing tasks.

PURPOSE: To compare radiation exposure of nurses when performing nursing tasks associated with interventional procedures depending on whether or not the nurses called out to the operator before approaching the patient. MATERIALS AND METHODS: In a prospective study, 93 interventional radiology procedures were randomly divided into a call group and a no-call group; there were 50 procedures in the call group and 43 procedures in the no-call group. Two monitoring badges were used to calculate effective dose of nurses. In the call group, the nurse first told the operator she was going to approach the patient each time she was about to do so. In the no-call group, the nurse did not say anything to the operator when she was about to approach the patient. RESULTS: In all the nursing tasks, the equivalent dose at the umbilical level inside the lead apron was below the detectable limit. The equivalent dose at the sternal level outside the lead apron was 0.16 µSv ± 0.41 per procedure in the call group and 0.51 µSv ± 1.17 per procedure in the no-call group. The effective dose was 0.018 µSv ± 0.04 per procedure in the call group and 0.056 µSv ± 0.129 per procedure in the no-call group. The call group had a significantly lower radiation dose (P = .034). CONCLUSIONS: Radiation doses of nurses were lower in the group in which the nurse called to the operator before she approached the patient.

Comparison of Tc-99m GSA scintigraphy and CT volumetry for evaluation in portal vein embolization.

PURPOSE: To determine the correlation of the rate of change of each future remnant liver (FRL) before and after portal vein embolization (PVE), by CT volumetry and Tc-99m galactosyl human serum albumin scintigraphy (GSA scintigraphy). MATERIAL AND METHODS: From December 2007 to July 2012, ten patients underwent PVE before hepatic resection. CT volumetry and GSA scintigraphy were performed before and after PVE. The FRL was divided at Cantlie's line for CT volumetry, and volume change rates before and after PVE were calculated. The maximum removal rate (Rmax) was calculated using a radiopharmacokinetic model in GSA scintigraphy. The FRL Rmax change rates before and after PVE were calculated. The correlation between the volume change rates and the Rmax change rates was analyzed. RESULTS: The FRL volume change rate was 1.28 ± 0.26 (mean ± SD); the FRL hypertrophied in all patients significantly (p = 0.005). The FRL Rmax change rate was 1.66 ± 0.75; excluding one patient, there was significant FRL Rmax increase (p = 0.022). Although both increased significantly, no correlation between the volume change rate and the Rmax change rate was observed. CONCLUSION: No correlation was observed between the FRL volume rate and the Rmax rate.

Diffusion-weighted echo-planar imaging of the head and neck using 3-T MRI: Investigation into the usefulness of liquid perfluorocarbon pads and choice of optimal fat suppression method.

PURPOSE: To investigate whether image quality can be improved using liquid perfluorocarbon pads (Sat Pad) and clarify the optimal fat-suppression method among chemical shift selective (CHESS), water excitation (WEX), and short TI inversion recovery (STIR) methods in diffusion-weighted imaging (DWI) of the head and neck using 3-T magnetic resonance imaging. Correlations between results of visual inspection and quantitative analysis were also examined. MATERIAL AND METHODS: This study was approved by our Institutional Review Board and informed consent was waived. DWI was performed on 25 subjects with/without Sat Pad and using three fat-suppression methods (6 patterns). Image quality was evaluated visually (4-point scales and lesion-depiction capability) and by quantitative analysis (signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)). Two-way repeated-measures analysis of variance (ANOVA) was used to detect significant differences in scores of visual evaluation, SNR, and CNR. RESULTS: Mean visual evaluation scores were significantly higher with Sat Pad using STIR than without Sat Pad for all fat-suppression methods (P<0.05). DWI with Sat Pad using STIR tended to be useful for depicting lesions. DWI using STIR showed reduced W-SNR (W: whole area of depicted structure) and CNR (between semispinalis capitis muscle and subcutaneous fat) due to fewer artifacts and uniform fat suppression. CONCLUSION: Combining Sat Pad with STIR provides good image quality for visual inspections. When numerous artifacts are present and fat suppression is insufficient, higher SNR and CNR do not always provide good diagnostic image quality.

Intra-arterial infusion of thrombin: animal experiments.

PURPOSE: Thrombin inhibits cadherin on vascular endothelial cells, rapidly and reversibly increasing endothelial permeability. The purpose of this study was to evaluate the feasibility of trans-arterial infusion with thrombin. MATERIAL AND METHODS: Ten rabbits with right thigh tumor were randomly divided into two groups: A thrombin group and a control group. In the thrombin group, a suspension of thrombin (300 IU), cisplatin (3 mg), lipiodol (0.3 ml) and iopamidol (0.3 ml) was infused into the right femoral artery. In the control group, a suspension of cisplatin, lipiodol and iopamidol was infused. Platinum concentrations in plasma were measured five and ten minutes after administration. Platinum concentrations were also measured in tumor specimens excised 30 minutes after infusion. RESULTS: At both five and ten minutes after infusion, platinum concentrations in plasma were significantly lower for the thrombin group than for the control group. Platinum concentration in tumor tissue was significantly higher for the thrombin group than for the control group. CONCLUSION: The present results suggest that transarterial infusion with thrombin may offer a number of pharmacological advantages.

Apolipoprotein C-II is a potential serum biomarker as a prognostic factor of locally advanced cervical cancer after chemoradiation therapy.

PURPOSE: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). METHODS AND MATERIALS: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization-time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. RESULTS: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). CONCLUSION: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.

An investigation of the early detection of radiation induced apoptosis by 99mTc-Annexin V and 201thallium-chloride in a lung cancer cell line.

This study aims to investigate the efficacy of in vitro Thallium-201 Chloride (Tl-201) and in vitro and in vivo Tc-99m HYNIC-coupled Annexin V (TAV) in the early detection of radiation induced apoptosis, a proxy indicator of radiation therapy (RT) efficacy. In vitro Tl-201 and TAV accumulation and efflux in non-small cell lung cancer were measured post irradiation at 5 different gamma ray doses. The replication rates (RR) of the cell lines were also measured. The same non-small cell lung cancer line was inoculated into the left femur. In vivo non-invasive Tl-201 and TAV tracer biodistribution studies were performed. Cell RR decrease with increased radiation dose was observed 48 hours after irradiation. Apoptotic cell number was found to have increased in response to 9 Gy and 12 Gy radiation dose. Tl-201 accumulation in the 9 Gy and 12 Gy irradiation groups was found to be higher than the lower irradiation groups. Quick Tl-201 efflux was observed in the 9 Gy and 12 Gy irradiated cells. At 48 hours after irradiation with 9 Gy and 12 Gy, Annexin V accumulation was found to be higher than in the control and 3-6 Gy groups. In vivo mouse model confirmed the increased TAV uptake in implanted tumors for relatively high 9 Gy irradiation as compared to non-irradiated controls. TAV may prove to be an effective radiotracer for early assessment of radiation therapy efficacy, via apoptosis, in human lung cancers.