Estimation of radioactivity in single photon emission computed tomography for sentinel lymph node biopsy in a torso phantom study

Objectives: Number of lymph nodes to be removed are determined from residual counts. Estimating residual radioactivity in lymphatic nodes before a biopsy in advance is useful for reducing surgical operation time. The purpose of this study was to estimate total radioactivity of a small hot spot in single-photon emission computed tomography (SPECT) of a torso phantom. Methods: Cross-calibration study was performed to convert counts in SPECT images to radioactivity. A simulation study was performed to estimate the size of volume of interest (VOI) covering a hot spot corrupted with full width at half maximum (FWHM) between 8 and 16 mm. The estimation of total radioactivity was validated in a torso phantom study using small sources. Results: True radioactivity was approximately equal to integrated values of hot spots using the VOI with a diameter of 40 mm in our simulation study. The difference was less than18% in cases of more than 9.4 kBq. Conclusions: The total radioactivity in small sources simulating a typical sentinel node was estimated from SPECT images using a VOI of 40 mm in a torso phantom study. Because the difference from actual values were less than 10% on average when radioactivities were more than 9.4 kBq, the total radioactivity of a lymph node can be estimated in a clinical examination

Environmental impact on star-forming galaxies in a z∼0.9z \sim 0.9 cluster during course of galaxy accretion

Galaxies change their properties as they assemble into clusters. In order to understand the physics behind that, we need to go back in time and observe directly what is occurring in galaxies as they fall into a cluster. We have conducted a narrow-band and $J$-band imaging survey on a cluster CL1604-D at $z=0.923$ using a new infrared instrument SWIMS installed at the Subaru Telescope. The narrow-band filter, NB1261, matches to H$\alpha$ emission from the cluster at $z=0.923$. Combined with a wide range of existing data from various surveys, we have investigated galaxy properties in and around this cluster in great detail. We have identified 27 H$\alpha$ emitters associated with the cluster. They have significant overlap with MIPS 24$\mu$m sources and are located exclusively in the star forming regime on the rest-frame $UVJ$ diagram. We have identified two groups of galaxies near the cluster in the 2D spatial distribution and the phase-space diagram, which are likely to be in-falling to the cluster main body. We have compared various physical properties of star forming galaxies, such as specific star formation rates (burstiness) and morphologies (merger) as a function of environment; cluster center, older group, younger group, and the field. As a result, a global picture has emerged on how the galaxy properties are altered as they assemble into a denser region. This includes the occurrence of mergers, enhancement of star formation activity, excursion to the dusty starburst phase, and eventual quenching to a passive phase.Comment: 19 pages, 15 figures. Accepted for publication in ApJ. Error bars in Table 2 correcte

Thermosensitive Polymer-Modified Liposome as a Multimodal and Multifunctional Carrier for MRI and Optical Imaging: Tumor Detection, Visualization of Triggered Drug Release, and Chemotherapy.

Introduction: A liposomal drug delivery system will be help to avoid the side effects of chemotherapy by releasing anticancer drug at the tumor site. Recently, using doxorubicin-containing lysolipid-based temperature-sensitive liposomes (Dox-LTSLs) it has been reported that tumor doxorubicin concentrations were up to 30 times higher than those of mice treated with free drug administration (1,2). The temporal and spatial pattern of drug delivery in a fibrosarcoma model was visualized during treatment using LTSLs containing doxorubicin and a MnSO4 MRI contrast agent(Dox/Mn-LTSLs) (3). Conventional thermosensitive liposomes, such as a gel-to-liquid-crystalline transition-based material, have the potential shortcoming that drug molecules may leak through the incomplete membrane of the liposome. On the other hand, our thermo-sensitive polymer-modified liposomes (TPL) can provide precise drug release using hydrophobicity change of the copolymer as a thermo-triggering (4).Dehydrated copolymer chains strongly destabilize the liposomal membrane within a limited temperature range (40-42C), and therefore the TPL provides both highly accurate temperature sensitivity and long-term stability in-vivo (8 hours). To improve the liposomal drug delivery system, we developed a multimodal-TPL (MTPL) and added three new factors, long-term stability of the liposome in-vivo, passive accumulation in the tumor, and multimodal in-vivo observation with both MRI and (fluorescent) optical imaging. The purpose of this study was to investigate whether 1) MRI and optical imaging can visualize accumulation of MTPL in the tumor after administration, 2) MTPL allows visualization of the drug release after beingtriggered by mild-heating (42.5C) eight hours after administration, and 3) MTPL can provide sufficient anti-tumor effects after treatment.Materials and Methods: EYPC, DOPE, Chol, PEG(2000)-PE, EOEOVE-ODVE and Rho-PE (23.4/54.6/15/4/2/1, mol%) (53.3 mg) were dissolved in a mixture of chloroform and methanol, and the solvent was removed by evaporation. The obtained thin lipid/copolymer-mixed membrane was further dried under vacuum for 4 h and dispersed in an aqueous MnSO4 solution (300 mM, pH5.3). ADR-loaded liposomes were purified using a Sepharose 4B column with a mixture of 20 mM Hepes and 150 mM NaCl (pH 7.4). Female Bulb/c nude mice (n = 13, 17.5 +- 2.5 g) were divided into three groups:heated group (n = 5), non-heated group (n = 5), and short-term observation group (n = 3). Colon 26 cancer cells were transplanted subcutaneously in the femurs of the mice under 2.0 % isoflurane anesthesia. Tumors were allowed to grow for 7 days before treatment. For both the heated and non-heated group, the MTPL (0.3 ml) was administrated via the tail vein under 2.0 % isoflurane anesthesia. In vivo optical imaging (IVIS-100 system, Caliper Life Sciences, CA) was performed 0, 4 and 8 hours after the MTPL administration under 2.0 % isoflurane anesthesia. For the heated group, transversal and horizontal multi-slice T1-weighted MR images (TR/TE = 250/9.57 ms, slice thickness = 1.5 mm, matrix = 256*256, field of view = 32.0 mm, average = 4) were acquired prior to heating using a 7.0 T-MRI (Magnet: Kobelco, Japan. Console: Bruker, Germany) in combination with a volume coil fortransmission (Bruker) and 2ch phased array coil for receiving (Rapid Biomedical, Germany) 8 hours after the MTPL administration. Thereafter, one side of the tumor site was heated at 42.5C for 10 minutes by hot-water circulation with temperature monitoring in the rectum and at the tumor site using a fiber optic thermometer. MRI acquisition was performed again in same manner after heating. For the short-term group, continuous MRI acquisitions were performed for 3 hours in the same manner and after MTPL administration inside the magnet under 1.5 % isoflurane anesthesia. Micewere allowed to recover from anesthesia after the MRI measurement and kept in normal cages for 14 days.Results and Discussion: MTPLs that contain doxorubicin for chemotherapy, MnSO4 as an MRI contrast agent, and the fluorescent dye Rhodamine for in-vivo optical imaging were synthesized (Fig. 1). Moderate signal enhancements on the T1-weighted MRI (Fig. 2) and definitive signals on the optical imaging (Fig. 3) were observed in the tumor after MTPL administration without heating. MRI signal intensity was further enhanced over an expanded area after mild-heating (42.5C) eight hours after the administration (Fig. 4, yellow arrows). The anti-tumor effect of the MTPL was clear for 14 days after the treatment (Fig. 5).Conclusions: We developed MTPLs and demonstrated long-term stability with tumor accumulatability. This method provides a system consisting of diagnostic, treatment, and evaluation methods. In addition, it will be useful for "active" targeting using antibodies or peptides with highly specific accumulation.ISMRM 16th Scientific Meeting and Exhibitio

Thermosensitive Polymer-modified Liposome as a Multimodal and Multifunctional Carrier for MRI and Optical Imaging:Tumor Detection, Visualization of Triggered Drug Release, and Chemotherapy

Introduction: A liposomal drug delivery system will be help to avoid the side effects of chemotherapy by releasing anticancer drug at the tumor site. Recently, using doxorubicin-containing lysolipid-based temperature-sensitive liposomes (Dox-LTSLs) it has been reported that tumor doxorubicin concentrations were up to 30 times higher than those of mice treated with free drug administration (1,2). The temporal and spatial pattern of drug delivery in a fibrosarcoma model was visualized during treatment using LTSLs containing doxorubicin and a MnSO4 MRI contrast agent(Dox/Mn-LTSLs) (3). Conventional thermosensitive liposomes, such as a gel-to-liquid-crystalline transition-based material, have the potential shortcoming that drug molecules may leak through the incomplete membrane of the liposome. On the other hand, our thermo-sensitive polymer-modified liposomes (TPL) can provide precise drug release using hydrophobicity change of the copolymer as a thermo-triggering (4).Dehydrated copolymer chains strongly destabilize the liposomal membrane within a limited temperature range (40-42C), and therefore the TPL provides both highly accurate temperature sensitivity and long-term stability in-vivo (8 hours). To improve the liposomal drug delivery system, we developed a multimodal-TPL (MTPL) and added three new factors, long-term stability of the liposome in-vivo, passive accumulation in the tumor, and multimodal in-vivo observation with both MRI and (fluorescent) optical imaging. The purpose of this study was to investigate whether 1) MRI and optical imaging can visualize accumulation of MTPL in the tumor after administration, 2) MTPL allows visualization of the drug release after beingtriggered by mild-heating (42.5C) eight hours after administration, and 3) MTPL can provide sufficient anti-tumor effects after treatment.Materials and Methods: EYPC, DOPE, Chol, PEG(2000)-PE, EOEOVE-ODVE and Rho-PE (23.4/54.6/15/4/2/1, mol%) (53.3 mg) were dissolved in a mixture of chloroform and methanol, and the solvent was removed by evaporation. The obtained thin lipid/copolymer-mixed membrane was further dried under vacuum for 4 h and dispersed in an aqueous MnSO4 solution (300 mM, pH5.3). ADR-loaded liposomes were purified using a Sepharose 4B column with a mixture of 20 mM Hepes and 150 mM NaCl (pH 7.4). Female Bulb/c nude mice (n = 13, 17.5 +- 2.5 g) were divided into three groups:heated group (n = 5), non-heated group (n = 5), and short-term observation group (n = 3). Colon 26 cancer cells were transplanted subcutaneously in the femurs of the mice under 2.0 % isoflurane anesthesia. Tumors were allowed to grow for 7 days before treatment. For both the heated and non-heated group, the MTPL (0.3 ml) was administrated via the tail vein under 2.0 % isoflurane anesthesia. In vivo optical imaging (IVIS-100 system, Caliper Life Sciences, CA) was performed 0, 4 and 8 hours after the MTPL administration under 2.0 % isoflurane anesthesia. For the heated group, transversal and horizontal multi-slice T1-weighted MR images (TR/TE = 250/9.57 ms, slice thickness = 1.5 mm, matrix = 256*256, field of view = 32.0 mm, average = 4) were acquired prior to heating using a 7.0 T-MRI (Magnet: Kobelco, Japan. Console: Bruker, Germany) in combination with a volume coil fortransmission (Bruker) and 2ch phased array coil for receiving (Rapid Biomedical, Germany) 8 hours after the MTPL administration. Thereafter, one side of the tumor site was heated at 42.5C for 10 minutes by hot-water circulation with temperature monitoring in the rectum and at the tumor site using a fiber optic thermometer. MRI acquisition was performed again in same manner after heating. For the short-term group, continuous MRI acquisitions were performed for 3 hours in the same manner and after MTPL administration inside the magnet under 1.5 % isoflurane anesthesia. Micewere allowed to recover from anesthesia after the MRI measurement and kept in normal cages for 14 days.Results and Discussion: MTPLs that contain doxorubicin for chemotherapy, MnSO4 as an MRI contrast agent, and the fluorescent dye Rhodamine for in-vivo optical imaging were synthesized (Fig. 1). Moderate signal enhancements on the T1-weighted MRI (Fig. 2) and definitive signals on the optical imaging (Fig. 3) were observed in the tumor after MTPL administration without heating. MRI signal intensity was further enhanced over an expanded area after mild-heating (42.5C) eight hours after the administration (Fig. 4, yellow arrows). The anti-tumor effect of the MTPL was clear for 14 days after the treatment (Fig. 5).Conclusions: We developed MTPLs and demonstrated long-term stability with tumor accumulatability. This method provides a system consisting of diagnostic, treatment, and evaluation methods. In addition, it will be useful for "active" targeting using antibodies or peptides with highly specific accumulation.ISMRM 16th Scientific Meeting and Exhibitio

Evaluation of selective tumor detection by clinical magnetic resonance imaging using antibody-conjugated superparamagnetic iron oxide

Active targeting by monoclonal antibodies (mAbs) combined with nanosize superparamagnetic iron oxide (SPIO) is a promising technology for magnetic resonance imaging (MRI) diagnosis. However, the clinical applicability of this technology has not been investigated using appropriate controls. It is important to evaluate the targeting technology using widely used clinical 1.5-Tesla MRI in addition to the high-Tesla experimental MRI. In this study, we measured mAb-conjugated dextran-coated SPIO nanoparticles (CMDM) in vivo using clinical 1.5-Tesla MRI. MRI of tumor-bearing mice was performed using a simple comparison between positive and negative tumors derived from the same genetic background in each mouse. The system provided significant tumor-targeting specificity of the target tumor. To the best of our knowledge, this is the first report on the specific detection of target tumors by mAb-conjugated SPIO using clinical 1.5-Tesla MRI. Our observations provide clues for reliable active targeting using mAb-conjugated SPIO in clinical applications