Radioisotope Method Research Articles

Abstract P3-01-02: A comparison of significance with indocyanine green fluorescence imaging method and computed tomography-lymphography in sentinel lymph node identification for early breast cancer patients

Abstract Background: Sentinel lymph nodes (SLN) biopsy has been established as a standard of care in the treatment of early breast cancer. This technique represents a minimally invasive, highly accurate method of axillary staging and is an alternative to conventional axillary lymph node dissection. The combination of the radioisotope and dye-staining methods is the most accurate way to identify sentinel lymph nodes. We had reported feasibility and safety of a new technique of SLN identification using fluorescence imaging of indocyanine green (ICG) injection without any need for training. Recently, SLN identification using computed tomography-lymphography (CTLG) has been reported in Japan. This study investigated the comparison of significance with fluorescence imaging method and CTLG. Patients and method: Between January 2013 and May 2015, 213 breast cancer patients without clinical evidence of lymph node metastasis were treated. On the day before the operation, CTLG was performed using 64-row multidetector CT. We performed an intradermal injection in the periareolar area, using 4 ml of contrast agent with 1 ml of local anesthetic. The contrasted lymph flow and SLN were identified in reconstructed three-dimensional imaging. The SLN spot was indicated by CT laser light navigator system. During the operation, fluorescence images were obtained using the fluorescence imaging system, Photpdynamic Eye (pde-neo, Hamamatsu Photonics Co., Japan). After 5 mg / 0.3ml ICG was injected intradermally in to the periareolar skin, lymphatic drainage was observed with fluorescence images. SLN biopsy was performed referring to the point by axillary compression technique by plastic device. Results: The median age of the 213 patients was 59 (range 28 – 87) years old. CTLG and fluorescence imaging was safely performed in all patients. CTLG could visualize lymphatic flow and accurately identify SLN in 189 (89 %) and 196 (92 %) cases, respectively, whereas fluorescence imaging identified successfully lymphatic flow and SLN in all patients. Fluorescence imaging with axillary compression technique was visually easy to identify the location of SLN on the axillary skin even in obese patients. Lymphatic flows of CTLG were completely consistent with those of fluorescence imaging. The number of SLN identified by CTLG was significantly lower than that by fluorescence imaging (1.1 vs. 1.6, p<0.01). Twenty seven patients (13%) were found to have lymph node metastases pathologically, and 7 of them had micrometastases of lymph node. In case of partial enhancement of SLN with CTLG, the rate of positive metastasis was significant higher compared to the cases of whole enhancement (p<0.01), however, even if enhancement is poor, about 70 % cases without metastasis are present. Conclusion: Both of fluorescence imaging and CTLG revealed easy and effective to detect SLN. The fluorescence imaging with fluorescence mapping showed strong fluorescence from all parts of the surgical field, which hindered identification of SLNs, and fluorescence imaging was more high detection rate of SLN. Citation Format: Abe H, Yamasaki K, Teramoto A, Yoneda K, Ogawa M, Kawasaki M, Kameyama M. A comparison of significance with indocyanine green fluorescence imaging method and computed tomography-lymphography in sentinel lymph node identification for early breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-02.

Cisplatin Induced Renal Insufficiency Measured by Glomerular Filtration Rate with 99mTc-DTPA and by using Serum Creatinine based Formulae: A Prospective Study.

Cisplatin also known as Cis-Diammine-Dichloroplatinum (CDDP) is a chemotherapeutic alkylating nephrotoxic agent. Thus, it is necessary to know if renal function is normal before starting chemotherapy. Glomerular Filtration Rate (GFR) can be assessed directly by using a radiopharmaceutical (dGFR). Estimated GFR (eGFR) method use, Serum Creatinine (SCR) levels in mathematical formulae such as Cockroft-Gault (CG) and abbreviated. Modified Diet in Renal Disease (aMDRD). The serum creatinine level is a function of GFR but is relatively insensitive for detecting early renal insufficiency. We aimed to correlate the incidence of Renal Insufficiency (RI) before and one month after completion of chemotherapy treatment by various methods. In this prospective study, we examined 64 patients with locally advanced head neck and uterine cervix cancers, before and one month after chemotherapy treatment with CDDP. Single agent CDDP was used with dose range between 35mg/m2 as concurrent weekly chemotherapy. Baseline RI was seen in 9.3% of patients by SCR levels, in 21.8% by the dGFR method, in 43.75% by the GFR-CG method and in 25% by the GFR-aMDRD formula. We considered GFR of <60 ml/min and SCR >1.5mg% as RI. After completion of treatment, the median RI was seen in 12.5% by SCR levels, 34.38% by dGFR method, 53.13% by GFR-CG method and 40.63% by GFR-aMDRD formula. None of the methods of GFR estimation showed statistically significant increase in RI one month after CDDP infusion. Only a weak correlation was seen between dGFR and eGFR based on SCR value (p=0.006). Baseline RI was detected in 12% more cases when measured by dGFR as compared with SCR level. However, mathematical formulae overestimated baseline RI as compared to dGFR. One month after completion of treatment with CDDP chemotherapy, RI increased in 10%-15% cases as detected by all the four evaluated methods. There is weak correlation between SCR and dGFR thus implicating the importance of dGFR in assessing RI. Thus, despite normal SCR levels, GFR by radioisotope method should also be done as pre-treatment workup for cisplatin based chemotherapy.

Significance of Sentinel Lymph Nodes with Low Gamma Counts in Breast Cancer Patients via Radioisotopic Sentinel Lymph Node Biopsy

Objective: Sentinel lymph node biopsy (SLNB), a standard diagnostic procedure worldwide, uses blue dye and/or radioisotopic methods to detect clinically node-negative breast cancer. With the latter method, we often experience axillary lymph nodes with extremely low levels of radioactivity, compared with the maximum radioactive nodes. Here, we investigated the significance and possibility of metastasis in low radioactive SLNs in patients with and without metastasis in maximum radioactive SLNs. Patients and methods: Between 2003 and 2011, we subjected a total of 453 breasts in 443 patients with earlystage invasive ductal carcinoma to SLNB using a combination of blue dye and radioisotopic methods. All lymph nodes detected via gamma -probe were considered SLNs and resected. Results: SLNs were identified in 452 (99.8%) of 453 cases; of these, SLN metastasis was pathologically diagnosed in 118 cases (26.1%). Two or more SLNs were detected in 232 (51.2%) of 453 cases; of these, 46 cases (19.8%) had SLNs with gamma counts < 10% of the maximum detected values. Metastasis was detected in these low-gamma-count SLNs in 4 of 453 cases (0.9%), even though no metastasis had been detected in SLNs with maximum radioactivity levels. Macrometastasis was pathologically demonstrated in 3 of 4 cases. Conclusion: We identified several cases of metastatic SLNs with very low radioactivity, despite a lack of metastasis in SLNs with maximum radioactivity. These findings indicate that the evaluation of SLNs with gamma counts < 10% of the patient maximum would provide more precise information about the axillary status and help to maintain a low SLNB false-negative rate.

Abstract 9805: Lack of Correlation Between HDL Level and Fecal Cholesterol in Multiple Mouse Models Suggests Importance of HDL Functionality in Atherosclerosis Attenuation

To circumvent the residual cardiovascular disease burden in patients receiving statin therapy, HDL-raising was suggested as a plausible approach. However, lack of benefits of CETP inhibitors, Torcetrapib and Dalcetrapib, despite substantial increase in HDL, and lack of efficacy of CER-001, an apoA-I mimetic, proved disappointing. Paradoxically, apoA-I Milano subjects with low HDL have reduced CVD risk. These findings shifted the focus from HDL level to HDL function. Promoting reverse cholesterol transport (RCT) is one of the main functions of HDL, which is measured in an in vivo assay as macrophage-derived fecal 3H-cholesterol. Non-radioisotopic method to quantitate fecal cholesterol (chol) as an RCT index was found to correlate with macrophage radioisotopic method in mice. Using this method, we carried out a number of studies in several mouse models, including C57Bl, apoA-I-Tg, LDLr KO, and ob/ob, using tool compounds, LXR and PPAR-α agonists, known to enhance RCT. Animals were treated with LXR and PPAR-α agonists alone or in combination, and lipid profile, HDL level, serum chol efflux, fecal chol, and, in appropriate animal models, aortic lipid contents were measured. In C57Bl mice, LXR agonist, T1317, raised HDL by 30%, while feno decreased HDL by 30%, but fecal chol showed a 2-fold increase in both cases. Interestingly, combination (comb) treatment with LXR and PPAR-α agonists did not change HDL, but fecal chol increased by 4.5-fold. HDL in apoA-I-Tg mice increased by 40%, 80%, and 80% in LXR, PPAR-α, and comb treated groups; respective fecal chol increases were 1.8, 1.8, and 5-fold, suggesting a lack of correlation between HDL level and fecal chol. LXR, PPAR-α, and comb-treated ob/ob mice showed 40%, 35%, and 40% rise in HDL, but 3-, 3-, and 20-fold increases in fecal chol, respectively. No correlations in HDL level and fecal chol contents were noticed in LDLr KO mice as well. Atherosclerosis attenuation by LXR and PPAR-α agonists in LDLr KO and ob.ob/LDLr DKO mice was associated with increased fecal chol, but not HDL level. These data suggest: a) a lack of correlation between HDL level and fecal chol; b) synergistic effect of LXR and PPAR-α agonists on RCT; c) reduced lesion area associated with increased fecal chol; and d) RCT influenced by additional mechanisms.

Multiscale Framework for Imaging Radiolabeled Therapeutics

The resistance of a tumor to a drug is the result of bulk properties of the tumor tissue as well as phenotypic variations displayed by single cells. Here, we show that radioisotopic detection methods, commonly used for tracking the tissue distribution of drug compounds, can be extended to the single-cell level to image the same molecule over a range of physical scales. The anticancer drug rituximab was labeled with short-lived radionuclides (89Zr/64Cu) and its accumulation at the organ level was imaged using PET in a humanized transgenic mouse model of non-Hodgkin’s lymphoma. To capture the distribution of the drug at a finer scale, tissue sections and single living cells were imaged using radioluminescence microscopy (RLM), a novel method that can detect radionuclides with single-cell resolution. In vivo PET images (24 h postinjection) showed that [89Zr]rituximab targeted the intended site of human CD20 expression, the spleen. Within this organ, RLM was used to resolve radiotracer accumulation in the splenic red pulp. In a separate study, RLM highlighted marked differences between single cells, with binding of the radiolabeled antibody ranging from background levels to 1200 radionuclides per cell. Overall, RLM images demonstrated significantly higher spatial resolution and sensitivity than conventional storage-phosphor autoradiography. In conclusion, this combination of PET and RLM provides a unique opportunity for exploring the molecular mechanism of drugs by tracking the same molecule over multiple physical scales, ranging from single living cells to organs substructures and entire living subjects.

Historical reconstruction of anthropogenic mercury input from sedimentary records: Yeongsan Estuary, South Korea

The rapid economic growth of the Republic of Korea (S. Korea) within the last half-century has resulted in a pronounced increase in anthropogenic Hg emission from coal combustion, oil refining, cement production, and waste incineration. The record of increasing atmospheric sources have been investigated with a historical reconstruction of Hg accumulation in 30 sediment cores collected from the Yeongsan Estuary. Within the last several decades, this region has undergone severe anthropogenic alteration, including the construction of an estuarine dam forming the Yeongsan Lake, and installation of numerous seawalls that eliminated vast tidal flats and restricted estuarine circulation. Total mercury concentrations (T-Hg) measured in sediments deposited after 1980 (23.2 ± 9.6 ng g−1; n = 273), were significantly higher than those reported for pre-industrial sediments (i.e. background values: 8.6 ± 2.7 ng g−1; n = 274). An extensive survey of surface samples show that T-Hg concentrations are highest above the dam, with a gradient to lower values further offshore. The concomitant timing of enrichment of T-Hg within the sedimentary record and increased National emissions in Korea suggests that regional sources dominate the input to the Yeongsan Estuary. This indicates that with sufficient regional historic emission data, T-Hg might be utilized as a geochronologic tool to aid in corroborating traditional radioisotopic methods.

The clinical usefulness of the intraoperative detection of sentinel lymph node metastases by a rapid RT-PCR system in patients with gastric cancer.

The incidence of pathological lymph node metastases in patients with gastric cancer is 5% to 10%, which means that approximately 90% of patients with gastric cancer may undergo unnecessary lymphadenectomy. The precise intraoperative diagnosis of sentinel lymph node (SN) metastases is essential. The purpose of the current study was to verify the usefulness of a rapid reverse transcriptase-polymerase chain reaction (RT-PCR) system compared with hematoxylin and eosin staining for such diagnoses. A total of 113 patients with clinical T1-T2 (cT1-T2) gastric cancer, including 73 patients with cT1cN0 disease with a tumor diameter <4 cm, were enrolled in the current study. SNs were identified by a radioisotope method. Carcinoembryonic antigen and cytokeratin 19 were used as markers for RT-PCR and the cutoff values were set using 1701 lymph nodes harvested from 157 patients with gastric cancer. SNs were detected in all 113 patients. Sensitivity and accuracy for detection by paraffin section were both 100% in patients with cT1 disease and were 60% and 90%, respectively, in patients with cT2 disease. The sensitivity of RT-PCR for the detection of pathological SN metastases was 92.3%. Furthermore, 11 patients had SN metastases detected only by RT-PCR, and these patients had frequent lymphatic invasion. Hematoxylin and eosin staining detected SN metastases in 6 of 73 patients with cT1cN0 gastric cancer; RT-PCR and frozen section detected SN metastases in 6 and 4 of these patients, respectively. Accordingly, the sensitivity of RT-PCR and frozen section for the detection of those pathological SN metastases were 100% and 66.6%, respectively. The rapid RT-PCR system appears to have clinical usefulness for the intraoperative detection of SN metastases in patients with gastric cancer.

Adsorption of Cd(II) ions at the hydroxyapatite/electrolyte solution interface

The study of the Cd(II) ions adsorption at the hydroxyapatite/electrolyte solution interface and the changes of the electrical double layer (EDL) structure in this system are presented. The adsorption of Cd(II) ions was calculated from the loss of their concentration from the solution using the radioisotope method. The adsorption was studied in the range of the initial concentration from 0.000001 to 0.001mol/dm3 and as the function of pH. The results of measurements of Cd(II) ions adsorption kinetics on hydroxyapatite were fitted using the pseudo-first, pseudo-second, and multiexponential modes to check which model describes this process in the best way. In addition, the main properties of the EDL, i.e., surface charge density and zeta potential were determined by the potentiometeric titration and electrophoresis measurements, respectively. The adsorption of Cd(II) ions at hydroxyapatite contributed to the increase of the zeta potential and also to the change of the double electrical layer structure.

Application of Plutonium Isotopes to the Sediment Geochronology of Coarse-Grained Sediments from Englebright Lake, California (USA)

The determination of sediment accumulation rates in environments with temporal variations in texture is challenging using traditional radioisotope methods, largely due to low activities associated with coarse sediments. This study used Englebright Lake, an impoundment in northern California, as a model system to examine the application of plutonium isotopes in lacustrine environments where the interlayering of coarse and fine sediments complicates the geochronology. Inductively coupled plasma mass spectrometry was used to quantify plutonium isotopes and low limits of detection allowed for the measurement of plutonium in sand, clay, and silt fractions. Although measurable levels of plutonium were found in sand fractions, over 75 % of the total plutonium activity was found in fine-grain-size fractions (<63 μm). Correlations between cesium-137 and plutonium activities in fine-grained sediments (r = 0.81–0.98, p < 0.005) suggest that plutonium isotopes may be substituted for cesium isotopes in coarse-grained sediments where cesium is typically below detectable levels. Sediment accumulation rates calculated from grain-size normalized plutonium activity profiles ranged from 6 to 145 cm year−1 in Englebright Lake and identified a sediment depocenter at the delta front upstream of Englebright Dam. Progradation of the delta front reflected changes in sediment supply from the watershed in response to flood events, whereas average annual accumulation responded to human impacts. This study extends the application of plutonium isotopes for sediment geochronology to aquatic environments dominated by coarse sediments and provides new information that contributes to a better understanding of the processes influencing sediment deposition in Englebright Lake.

Optimizing scintigraphic evaluation of split renal function in living kidney donors using the geometric mean method: a preliminary retrospective study.

Accurate assessment of pre-transplant split renal function in candidates for living kidney donation is indispensable for side-selection and a sufficient long-term residual renal function. To analyse the need of depth correction in the assessment of split renal function in potential living kidney donors. In 13 consecutive patients screened for living kidney donation split renal function was measured with four different methods including conventional posterior MAG-3-scintigraphy, the geometric mean method in MAG-3-scintigraphy, MAG-3-scintigraphy with CT-based depth correction and CT-volumetry. Correlation and agreement of methods were analyzed using Spearman's rho correlation coefficient and the Bland-Altman method. Despite good correlation and agreement between the different radioisotopic methods there were clinically relevant differences in split renal function in 2/13 patients (15%) between conventional posterior MAG-3 scan and the geometric mean method. The best correlation was found between the two scintigraphic methods with depth correction. Comparing radioisotopic methods with CT-volumetry, significant differences were found in up to 6/13 patients (46%). Our results clearly indicate that in the case of living kidney donation further assessment concerning the accuracy and reliability of measuring split renal function is necessary. As there are no differences in duration of examination, costs and radiation exposure between techniques with and without depth correction, but clinically relevant differences in up to 46% of patients, kidney depth should be incorporated in daily clinical practice of living kidney donor evaluation. The geometric mean method could significantly improve future patient assessment in cases of living kidney donation.

Validation of Contrast Enhanced Ultrasound Technique to Wire Localization of Sentinel Lymph Node in Patients with Early Breast Cancer.

Axillary staging is one of the primary steps in management of Breast cancer patients. Current standard methods including blue dye and radicolloid have limitations and disadvantages. In this study, the feasibility of visualization of lymph node pathways and localization of SLN with the help of CEUS was assessed. 50 patients with early breast cancer diagnosis underwent CEUS and wire localization, methylenblue dye, and isotope scan methods for SLN detection. The pathology findings of the wired SLN were compared with those obtained from, methylenblue dye, and isotope scan methods. Lymph node wiring was successfully performed in 48 patients.Radio-isotope technique detected SLN in all 50 patients while blue-dye succeeded in 48. Sensitivity of CEUS to detect SLN compared with radio-isotope and blue dye methods was 96% and 100%, respectively. Considering costs and facilities required to perform radio-isotope technique and complications of blue dye we may accept CEUS with the help of micro-bubble contrasts as a viable alternative. However, more studies with larger sample volumes, using various drugs, and including non-selective population are warranted to better clarify feasibility and accuracy of this technique in comparison with current methods.

Drug action of benzocaine on the sarcoplasmic reticulum Ca-ATPase from fast-twitch skeletal muscle.

The effect of the local anesthetic benzocaine on sarcoplasmic reticulum membranes isolated from fast-twitch muscles was tested. The effects on Ca-ATPase activity, calcium binding and uptake, phosphoenzyme accumulation and decomposition were assessed using radioisotopic methods. The calcium binding to the Ca-ATPase was noncompetitively inhibited, and the enzymatic activity decreased in a concentration-dependent manner (IC50 47.1mM). The inhibition of the activity depended on the presence of the calcium ionophore calcimycin and the membrane protein concentration. The pre-exposure of the membranes to benzocaine enhanced the enzymatic activity in the absence of calcimycin, supporting the benzocaine permeabilizing effect, which was prevented by calcium. Benzocaine also interfered with the calcium transport capability by decreasing the maximal uptake (IC50 40.3mM) without modification of the calcium affinity for the ATPase. It inhibited the phosphorylation of the enzyme, and at high benzocaine concentration, the dephosphorylation step became rate-limiting as suggested by the biphasic profile of phosphoenzyme accumulation at different benzocaine concentrations. The data reported in this paper revealed a complex pattern of inhibition involving two sites for interaction with low and high benzocaine concentrations. It is concluded that benzocaine not only exerts an indirect action on the membrane permeability to calcium but also affects key steps of the Ca-ATPase enzymatic cycle.

Comparative 230Th/U and 14C Dating of a Buried Stump Layer (Western Siberia)

Abstract Dating of late Pleistocene sediments remains a challenge in Quaternary chronology, due to the inherent limitations of the 14C and OSL methods. The 230Th/U radioisotope method is theoretically applicable to wood remnants contained within Pleistocene sediments, but few results have been pub-lished to date and in some cases, the age data are ambiguous. This paper tests the use of 230Th/U da-ting of fossil wood remnants dated earlier by radiocarbon method. We analyzed a buried larch trunk from a well-known stump layer in the Lipovka outcrop, located on the Tobol River bank in Western Siberia. The stump layer is preserved in situ. We determined the specific activities of U and Th iso-topes in samples of both modern pine and fossil larch and proposed a model for the incorporation and distribution of U and Th in the buried wood during aging. Complications related with the recognition of geochemical closed systems with respect to U did not allow obtaining completely reliable 230Th/U age. Despite this the 230Th/U age obtained for the uppermost heartwood sample and 14C ages of the same larch trunk and other wood and vegetation remnants gave consistent results. These age data in combination with previously obtained pollen data testify the stump layer formation during the late cooling stage of the Karganian time (MIS-3, Middle Valdai).

Penetration of inhaled pollen into the respiratory tract.

The pathophysiologic mechanisms of pollen-induced asthma have heretofore remained unclear, because pollen particles have generally been considered too large to penetrate into the lower respiratory tract. Such grains are therefore believed to be unable to induce an immunologic response in the lower respiratory tract. Nevertheless, experimental curves of particle penetration into the respiratory tract indicate that a small percentage of large-sized particles may penetrate into the peripheral areas of the lungs. Under the conditions of our study, a radioisotopic method using labeled pollen grains was not effective in detecting the very small number of grains expected to be found in the lung. We used another simpler and more effective method derived from techniques used by palynologists in the detection of pollen grains in sediments. According to our results, which showed pollen grains normally present in tracheobronchial secretions and in lung parenchyma, we can safely assume that inhaled pollen does penetrate into the distal lower respiratory tract. At present, we do not know the precise number of pollen grains necessary to trigger a response, and we do not know the behavior of these grains with regard to the mucous membranes of the small bronchi and the alveoli. It is important to determine whether these grains have an effect on these areas and whether a direct mechanism is involved in the genesis of pollen-induced asthma.

Thermal analysis of hydroxyapatite with adsorbed oxalic acid

The specific adsorption of oxalic acid ions at the hydroxyapatite interface was investigated by means of the radioisotope method (14C) as a function of oxalic acid ions concentration, NaCl concentration and pH. Application of hydroxyapatite has become extensive in the biomaterial field due to its biocompatibility with human hard tissue. Hydroxyapatite was synthesized using wet methods. Physical properties of the resulting powder were characterized by DTA/TG, XRD, AFM and SEM microscopy. Physicochemical properties characterizing the electrical double layer of the hydroxyapatite/NaCl solution interface were determined. The zeta potential and the adsorption of oxalic acid molecules were studied as a function of pH. The point of zero charge and the isoelectric point of samples were determined: its values are as follows: pHPZC = 7 and pHIEP = 4. Temperature has insignificant influence on pure substance and with oxalic acid adsorbed, as thermal analysis has shown, and characterization of hydroxyapatite structure can be carried out by this thermal analysis. Two phenomena are responsible for oxalic acid adsorption: phosphate group replacement at the hydroxyapatite surface by oxalic ions simultaneous to intraspherical complexes formation.

Abstract P2-01-24: Sentinel lymph node biopsy using intraoperative indocyanine green fluorescence imaging navigated with preoperative computed tomography lymphography for early breast cancer

Abstract Background: Sentinel lymph nodes (SLN) biopsy has been established as a standard of care in the treatment of early breast cancer. The combination of the radioisotope and dye-staining methods is the most accurate way to identify sentinel lymph nodes. We had reported a novel technique of SLN identification using fluorescence imaging of indocyanine green (ICG) injection. However, if any lymphatic vessels are injured, further fluorescence navigation will be difficult because of ICG contamination in the surgical field in overweight or obese patients. In this study, a new diagnostic approach for imaging lymphatic drainage and identifying SLN using preoperative computed tomography-lymphography (CTLG) and an intraoperative ICG fluorescence method was investigated. Patients and method: Between January 2013 and April 2014,105 breast cancer patients without clinical evidence of lymph node metastasis were treated. On the day before the operation, CTLG was performed using 64-row multidetector CT. We performed an intradermal injection in the periareolar area, using 4 ml of contrast agent with 0.5 ml of local anesthetic. The contrasted lymph flow and SLN were identified in reconstructed three-dimensional imaging. The SLN spot was indicated by CT laser light navigator system. During the operation, fluorescence images were obtained using the fluorescence imaging system, Photpdynamic Eye (pde-neo, Hamamatsu Photonics Co., Japan). After ICG was injected intradermally in to the periareolar skin, lymphatic drainage was observed with fluorescence images. SLN biopsy was performed by referring to the marker preoperatively placed on the CTLG. Moreover, we classified enhancement of SLN as "whole" and "partial" by CTLG with visual patterns, and examined the relation with SLN metastasis. Results: The median age of the 105 patients was 63 (range 33 – 87) years old. CTLG and fluorescence imaging was safely performed in all patients. This method was visually easy to identify the location of SLN on the axillary skin even in obese patients. CTLG could visualize lymphatic flow and accurately identify SLN in 99 (94%) of 105 patients, whereas fluorescence imaging identified successfully lymphatic flow and SLN in all patients. Lymphatic flows of CTLG were completely consistent with those of fluorescence imaging. The number of SLN identified by CTLG was significantly lower than that by fluorescence imaging (1.1 vs. 1.6, p&amp;lt;0.01). Fifteen patients (14%) were found to have lymph node metastases pathologically, and five of them had micrometastases of lymph node. In 6 patients without detected SLN by CTLG, only one patient had lymph node metastasis. In case of partial enhancement of SLN with CTLG, the rate of positive metastasis was significant higher compared to the cases of whole enhancement (p&amp;lt;0.01). Enhancement of SLNs by CTLG Metastasis(+)Metastasis(-)Whole459Partial1026Not identified15 Conclusion: This new navigation method of CTLG and fluorescence imaging revealed more easy and effective to detect SLN intraoperatively than fluorescence imaging alone. In addition, the information from CTLG may be helpful for the prediction of SLN metastasis. Citation Format: Hajime Abe, Keiichi Yamazaki, Masao Ogawa, Masayasu Kawasaki, Kohri Yoneda, Masao Kameyama. Sentinel lymph node biopsy using intraoperative indocyanine green fluorescence imaging navigated with preoperative computed tomography lymphography for early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-24.

Preferentially examined sentinel nodes for sentinel node navigation surgery in gastric cancer.

The intraoperative examination of the sentinel nodes (SNs) is crucial for correctly performing SN navigation surgery (SNNS). Frozen-section diagnosis is ordinarily used; however, when several SNs are being assessed in gastric cancer, which has numerous regional lymph nodes, it is difficult to examine them all correctly within the short duration of surgery. In the present study, we aimed to determine the SNs that should be preferentially examined during SNNS in gastric cancer. A total of 824 SNs were examined in 113 patients with clinically determined T1-2 gastric cancer and no apparent lymph node metastasis. We focused on the accumulation of tracers expressed by hot nodes (HNs) using the radioisotope (RI) method and green nodes (GNs) using the dye-guided method and measured the radioactivity count of the HNs (RI count). We compared these parameters between 35 metastatic and 789 non-metastatic SNs. The percentage of metastasis-positive SNs that were radioactively 'hot' and dyed green was higher compared with that of the negative SNs (89 vs. 43%, respectively; P<0.01). The RI counts of the metastasis-positive SNs were higher compared with those of the negative SNs [median (range): 361 (0-10,670) vs. 53 (0-9,931), respectively; P<0.01]. The area under the receiver operating characteristic curve of the RI count was 0.69 (95% CI: 0.60-0.78). Therefore, when assessing several SNs, those with higher RI counts (HNs and GNs) should be preferentially examined. Further accumulation of cases is required to establish the cut-off value for the diagnosis of metastasis based on the RI count.

Radioisotope method of compound flow analysis

The paper presents gamma radiation application to analysis of a multicomponent or multiphase flow. Such information as a selected component content in the mixture transported through pipe is crucial in many industrial or laboratory installations. Properly selected sealed radioactive source and collimators, deliver the photon beam, penetrating cross section of the flow. Detectors mounted at opposite to the source side of the pipe, allow recording of digital signals representing composition of the stream. In the present development of electronics, detectors and computer software, a significant progress in know-how of this field may be observed. The paper describes application of this method to optimization and control of hydrotransport of solid particles and propose monitoring facilitating prevent of a pipe clogging or dangerous oscillations.

Axillary lymph node recurrence after sentinel lymph node biopsy performed using a combination of indocyanine green fluorescence and the blue dye method in early breast cancer.

There is limited information on indocyanine green (ICG) fluorescence and blue dye for detecting sentinel lymph node (SLN) in early breast cancer. A retrospective study was conducted to assess the feasibility of an SLN biopsy using the combination of ICG fluorescence and the blue dye method. Seven hundred and fourteen patients with clinically node-negative breast cancer were included in this study. They underwent SLN biopsy using a combination of ICG fluorescence and the blue dye method from March 2007 to February 2014. The ICG (a fluorescence-emitting source) and patent blue (the blue dye) were injected into the patients' subareolar region. The removed lymph nodes that had ICG fluorescence and/or blue dye uptake were defined as SLNs. The results of the SLN biopsies and follow-up results of patients who underwent SLN biopsy alone were investigated. In 711 out of 714 patients, SLNs were identified by a combination of ICG fluorescence and the blue dye method (detection rate, 99.6 %). The average number of SLNs was 2.4 (range 1-7), and the average number of resected swollen para-SLNs was 0.4 (range 0-5). Ninety-nine patients with an SLN and/or para-SLN involvement during the intraoperative pathological diagnosis underwent axillary lymph node resection (ALND). In addition, two of three patients whose SLN was not identified also underwent ALND. In 46 of 101 patients with an ALND, non-SLN involvement was not found. Follow-up results were analyzed in 464 patients with invasive carcinoma excluding those with ductal carcinoma in situ (n = 148) and those who underwent ALND (n = 101). During the follow-up period (range 4.4-87.7 months; median, 38 months), two patients (0.4 %) developed axillary lymph node recurrence. They were successfully salvaged, and to date, no further locoregional recurrence has been observed. A high rate of SLN detection and low rate of axillary lymph node recurrence were confirmed by an SLN biopsy using a combination of ICG fluorescence and the blue dye method. Therefore, it is suggested that this method may replace the combination of dye and radioisotope methods.

A radioisotope-nondependent high-sensitivity method for measuring the activity of glioblastoma-related O6-methylguanine DNA methyltransferase

O6-Methylguanine DNA methyltransferase (MGMT) cancels the anticancer effect of temozolomide (drug for glioblastoma), which introduces methylation to DNA. Therefore, developing an MGMT inhibitor is a promising strategy for the treatment of this cancer. For this purpose, a sensitive detection method that does not depend on the conventional radioisotope (RI) method was developed. This was realized by a fluorescence-based method that measured the amount of cleavable restriction sites demethylated by the action of MGMT; this method was enhanced by introducing a polymerase chain reaction (PCR) amplification step. As an assay of enzyme activity, 20-fold higher sensitivity (subnanomolar) was attained compared with our and others’ fluorescence-based approaches.