Satoshi Watanabe

Deoxymugineic acid increases Zn translocation in Zn-deficient rice plants.

Deoxymugineic acid (DMA) is a member of the mugineic acid family phytosiderophores (MAs), which are natural metal chelators produced by graminaceous plants. Rice secretes DMA in response to Fe deficiency to take up Fe in the form of Fe(III)–MAs complex. In contrast with barley, the roots of which secrete MAs in response to Zn deficiency, the amount of DMA secreted by rice roots was slightly decreased under conditions of low Zn supply. There was a concomitant increase in endogenous DMA in rice shoots, suggesting that DMA plays a role in the translocation of Zn within Zn-deficient rice plants. The expression of OsNAS1 and OsNAS2 was not increased in Zn-deficient roots but that of OsNAS3 was increased in Zn-deficient roots and shoots. The expression of OsNAAT1 was also increased in Zn-deficient roots and dramatically increased in shoots; correspondingly, HPLC analysis was unable to detect nicotianamine in Zn-deficient shoots. The expression of OsDMAS1 was increased in Zn-deficient shoots. Analyses using the positron-emitting tracer imaging system (PETIS) showed that Zn-deficient rice roots absorbed less 62Zn-DMA than 62Zn2+. Importantly, supply of 62Zn-DMA rather than 62Zn2+ increased the translocation of 62Zn into the leaves of Zn-deficient plants. This was especially evident in the discrimination center (DC). These results suggest that DMA in Zn-deficient rice plants has an important role in the distribution of Zn within the plant rather than in the absorption of Zn from the soil.

52Fe Translocation in Barley as Monitored by a Positron-Emitting Tracer Imaging System (PETIS) : Evidence for the Direct Translocation of Fe from Roots to Young Leaves via Phloem

The real-time translocation of iron (Fe) in barley (Hordeum vulgare L. cv. Ehimehadaka no. 1) was visualized using the positron-emitting tracer 52Fe and a positron-emitting tracer imaging system (PETIS). PETIS allowed us to monitor Fe translocation in barley non-destructively under various conditions. In all cases, 52Fe first accumulated at the basal part of the shoot, suggesting that this region may play an important role in Fe distribution in graminaceous plants. Fe-deficient barley showed greater translocation of 52Fe from roots to shoots than did Fe-sufficient barley, demonstrating that Fe deficiency causes enhanced 52Fe uptake and translocation to shoots. In the dark, translocation of 52Fe to the youngest leaf was equivalent to or higher than that under the light condition, while the translocation of 52Fe to the older leaves was decreased, in both Fe-deficient and Fe-sufficient barley. This suggests the possibility that the mechanism and/or pathway of Fe translocation to the youngest leaf may be different from that to the older leaves. When phloem transport in the leaf was blocked by steam treatment, 52Fe translocation from the roots to older leaves was not affected, while 52Fe translocation to the youngest leaf was reduced, indicating that Fe is translocated to the youngest leaf via phloem in addition to xylem. We propose a novel model in which root-absorbed Fe is translocated from the basal part of the shoots and/or roots to the youngest leaf via phloem in graminaceous plants.

52Mn translocation in barley monitored using a positron‐emitting tracer imaging system

Abstract Until now, the real-time uptake and movement of manganese (Mn), an essential plant nutrient, has not been documented in plants. In this study, the real-time translocation of Mn in barley (Hordeum vulgare L. cv. Ehimehadaka no. 1) was visualized using the positron-emitting tracer 52Mn and a positron-emitting tracer imaging system (PETIS). PETIS allowed the non-destructive monitoring of Mn translocation in barley under various conditions. In all cases, 52Mn first accumulated in the discrimination center (DC) at the basal portion of the shoot, suggesting that this region may play an important role in Mn distribution in graminaceous plants. Manganese-deficient barley showed greater translocation of 52Mn from roots to shoots than did Mn-sufficient barley, demonstrating that Mn deficiency causes enhanced Mn uptake and loading into vascular bundles. In contrast, the translocation of 52Mn from roots to shoots was suppressed in Mn-excess barley. In these plants, the uptake of Mn may be suppressed or Mn may accumulate in the intercellular organelles of root cells, resulting in low rates of Mn translocation to shoots. In Mn-sufficient barley, the dark treatment did not suppress the translocation of 52Mn to the youngest leaf, suggesting that the translocation of Mn to the youngest leaf is independent of the transpiration stream. When 52Mn was supplied to the cut end of an expanded leaf, 52Mn was transported to the DC within 27 min and then retranslocated to roots and other leaves. Our results show that the translocation of Mn from the roots to the DC depends passively on water flow, but actively on the Mn transporter(s).

Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with 64Cu-labeled trastuzumab PET

Non‐small cell lung carcinomas (NSCLC) overexpress the Her2/neu gene in approximately 59% of cases. Trastuzumab, a humanized monoclonal antibody, interferes with Her2 signaling and is approved for the treatment of Her2/neu overexpressing breast cancer. However, its therapeutic use in Her2/neu overexpressing NSCLC remains obscure. The present study aimed to determine the role of 64Cu‐labeled trastuzumab positron emission tomography (PET) for non‐invasive imaging of Her2/neu expression in NSCLC. Trastuzumab was conjugated with the bifunctional chelator 1, 4, 7, 10‐tetraazacyclododecane‐1, 4, 7, 10‐tetraacetic acid (DOTA) and radiolabeled with 64Cu. The molecular specificity of DOTA‐trastuzumab was determined in NSCLC cell lines with Her2/neu overexpression (NCI‐H2170) and negative expression (NCI‐H520). Imaging of Her2/neu expression was performed in NCI‐H2170 tumor‐bearing mice with 64Cu‐DOTA‐trastuzumab PET and 64Cu‐DOTA‐IgG. In vitro studies revealed specific binding of DOTA‐trastuzumab in the Her2/neu positive NCI‐H2170 cells, while no binding was seen in the Her2/neu negative NCI‐H520 cell line. Biodistribution and PET studies revealed a significantly high accumulation of 64Cu‐DOTA‐trastuzumab in the Her2/neu overexpressing NCI‐H2170 tumor at 24 and 48u2003h post‐injection (21.4u2003±u20031.4% and 23.2u2003±u20035.1% injection dose/gram (% ID/g), respectively). PET imaging of Her2/neu negative NCI‐H520 tumors showed much less uptake of 64Cu‐DOTA‐trastuzumab (4.0% ID/g). The NCI‐H2170 tumor uptake of 64Cu‐DOTA‐trastuzumab was significantly higher than that of 64Cu‐DOTA‐IgG (Pu2003<u20030.0001). 64Cu‐DOTA‐trastuzumab showed a very clear image of a Her2/neu positive tumor and appeared to be effective as a PET tracer for imaging of Her2/neu gene expression in NSCLC, suggesting its potential clinical use for identifying patients that might benefit from trastuzumab‐based therapy.

Multiplet Structures of Transition Metal Deep Impurities in ZnS

The electronic structures of substitutional 3d transition metal (TM) impurities Ti 2+ to Cu 2+ in ZnS have been calculated from the first principles in the cluster method. The TM impurity states are found to be described well by a relatively large cluster consisting of 59 atoms. All impurity states appear in the energy gap region of ZnS and have a strong TM 3d character except those of Cu 2+ . The effects of multiplet struclure have been included by a parameter-free approach which connects the first principles results with the ligand field theory. The low-lying multiplets of 3d TM impurities in ZnS are reproduced well by the present theory.

Production of highly purified no-carrier-added 177Lu for radioimmunotherapy

No-carrier-added 177Lu produced via the 176Yb(n, γ)177Ybxa0→xa0177Lu process was separated from the macroscopic amounts of the Yb target using reversed-phase ion-pair liquid chromatography. To produce a highly purified 177Lu solution capable of labeling antibodies, the metallic impurities were removed using cation, chelating ion, and anion exchange columns. After the elimination of metallic impurities, the concentrations of Ca, Fe, and Zn were reduced from 87, 340, and 77xa0ppb to 13, 18, and 9xa0ppb, respectively. Consequently, the labeling yield of the 177Lu-labeled antibody increased from <5 to 88xa0%.

First Measurement of the Radionuclide Purity of the Therapeutic Isotope 67Cu Produced by 68Zn(n,x) Reaction Using natC(d,n) Neutrons

We have for the first time studied the radionuclide purity of the therapeutic isotope 67Cu produced by the 68Zn(n,x)67Cu reaction. The neutrons were obtained by the natC(d,n) reaction using 40 MeV ...

Preparation and biological evaluation of 3-[76Br]bromo-α-methyl-l-tyrosine, a novel tyrosine analog for positron emission tomography imaging of tumors

INTRODUCTIONn3-[(18)F]fluoro-α-methyl-l-tyrosine ([(18)F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. FAMT analogs labeled with (76)Br, a positron emitter with a long half-life (t(1/2)=16.1 h), could potentially be widely used as amino acid tracers for tumor imaging. In this study, 3-[(76)Br]bromo-α-methyl-l-tyrosine ([(76)Br]BAMT) was designed, and its usefulness was evaluated as a novel PET tracer for imaging malignant tumors.nnnMETHODSnIn this study, both [(76)Br]BAMT and [(77)Br]BAMT were prepared. The in vitro and in vivo stability of [(77)Br]BAMT was evaluated by HPLC analysis. Cellular uptake and retention of [(77)Br]BAMT and [(18)F]FAMT were evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in normal mice and in LS180 tumor-bearing mice, and the tumors were imaged with a small-animal PET scanner.nnnRESULTSn[(77)Br]BAMT was stable in vitro but was catabolized after administration in mice. Cellular accumulation and retention of [(77)Br]BAMT were significantly higher than those of [(18)F]FAMT. In biodistribution studies, the tumor accumulation of [(77)Br]BAMT was higher than that of [(18)F]FAMT. However, some level of debromination was seen, which caused more retention of radioactivity in the blood and organs than was seen with [(18)F]FAMT. PET imaging with [(76)Br]BAMT enabled clear visualization of the tumor, and the whole-body image using [(76)Br]BAMT was similar to that using [(18)F]FAMT.nnnCONCLUSIONSn[(77)Br]BAMT showed high levels of tumor accumulation, and [(76)Br]BAMT enabled clear visualization of the tumor by PET imaging. Although an improvement in stability is still needed, (76)Br-labeled FAMT analogs could potentially serve as PET tracers for the imaging of malignant tumors.

Basic characteristics of a newly developed Si/CdTe Compton camera for medical imaging

We have developed a prototype Compton camera for in vivo imaging by using semiconductor imaging devices, which has been proved to be successful techniques for the observation of high-energy astrophysical phenomena. In this camera, double-sided Si strip detectors (DSSDs) serve as scatterers and pixelized CdTe detectors (pCdTe) serve as absorbers. Some Compton images were acquired with radioisotopes in a phantom, which reveal certain characteristics of the field of view this camera, and the distributions of efficiencies and spatial resolutions. In a rat study, the nuclides in the body were distinguished by their γ-ray energies, and the difference in the distributions of the nuclides could also be successfully observed.

Lutetium-177 complexation of DOTA and DTPA in the presence of competing metals

As part of basic studies on bifunctional chelating agents for 177Lu-labeled antibodies, 177Lu complexation of 1,4,7,10-tetraazacyclododecan-N,N´,N´´,N´´´-tetraacetic acid (DOTA) and diethylenetriamine-N,N,N´,N´´,N´´-pentaacetic acid (DTPA) was investigated in the presence of competing metals, including Ca(II), Fe(II), and Zn(II). It was found that DTPA is a better 177Lu complexation agent than DOTA in the presence of Ca(II), Fe(II), and Zn(II). Moreover, the elimination of Fe from the 177Lu solution proved especially effective because the DTPA comlexation of 177Lu was highly inhibited by Fe(II).