Α. Türler

The superheavy element with atomic number Z 117 was produced as an evaporation residue in the 48 Ca 249 Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their -decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-s and a few days. Two decay chains comprising seven decays and a spontaneous fission each were identified and are assigned to the isotope 294 117 and its decay products. A hitherto unknown -decay branch in 270 Db (Z 105) was observed, which populated the new isotope 266 Lr (Z 103). The identification of the long-lived (T 1=2 1.0 1.9 -0.4 h) -emitter 270 Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."

OBJECTIVE: To investigate the initiation of a complex inflammatory response within the human intestinal muscularis intraoperatively so as to determine the clinical applicability of the inflammatory hypothesis of postoperative ileus. SUMMARY BACKGROUND DATA: Mild intestinal manipulation in rodents initiates the activation of transcription factors, upregulates proinflammatory cytokines, and increases the release of kinetically active mediators (nitric oxide and prostaglandins), all of which results in the recruitment of leukocytes and a suppression in motility (i.e., postoperative ileus). METHODS: Human small bowel specimens were harvested during abdominal procedures at various times after laparotomy. Histochemical and immunohistochemical techniques were applied to intestinal muscularis whole-mounts. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed for interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Signal transducers and activators of transcription (STAT) protein phosphorylation was determined by electromobility shift assay. Organ bath experiments were performed on jejunal circular smooth muscle strips. GW274150C and DFU were used in vitro as iNOS and COX-2 inhibitors. RESULTS: Normal human muscularis externa contained numerous macrophages that expressed increased lymphocyte function associated antigen-1 (LFA-1) immunoreactivity as a function of intraoperative time. RT-PCR demonstrated a time-dependent induction of IL-6, IL-1beta, TNF-alpha, iNOS, and COX-2 mRNAs within muscularis extracts after incision. Mediators were localized to macrophages with STAT protein activation in protein extracts demonstrating local IL-6 functional activity. DFU alone or in combination with GW274150C increased circular muscle contractility. Specimens harvested after reoperation developed leukocytic infiltrates and displayed diminished in vitro muscle contractility. CONCLUSIONS: These human data demonstrate that surgical trauma is followed by resident muscularis macrophage activation and the upregulation, release, and functional activity of proinflammatory cytokines and kinetically active mediators.

UNLABELLED: Terbium offers 4 clinically interesting radioisotopes with complementary physical decay characteristics: (149)Tb, (152)Tb, (155)Tb, and (161)Tb. The identical chemical characteristics of these radioisotopes allow the preparation of radiopharmaceuticals with identical pharmacokinetics useful for PET ((152)Tb) and SPECT diagnosis ((155)Tb) and for α- ((149)Tb) and β(-)-particle ((161)Tb) therapy. The goal of this proof-of-concept study was to produce all 4 terbium radioisotopes and assess their diagnostic and therapeutic features in vivo when labeled with a folate-based targeting agent. METHODS: (161)Tb was produced by irradiation of (160)Gd targets with neutrons at Paul Scherrer Institute or Institut Laue-Langevin. After neutron capture, the short-lived (161)Gd decays to (161)Tb. (149)Tb, (152)Tb, and (155)Tb were produced by proton-induced spallation of tantalum targets, followed by an online isotope separation process at ISOLDE/CERN. The isotopes were purified by means of cation exchange chromatography. For the in vivo studies, we used the DOTA-folate conjugate cm09, which binds to folate receptor (FR)-positive KB tumor cells. Therapy experiments with (149)Tb-cm09 and (161)Tb-cm09 were performed in KB tumor-bearing nude mice. Diagnostic PET/CT ((152)Tb-cm09) and SPECT/CT ((155)Tb-cm09 and (161)Tb-cm09) studies were performed in the same tumor mouse model. RESULTS: Carrier-free terbium radioisotopes were obtained after purification, with activities ranging from approximately 6 MBq (for (149)Tb) to approximately 15 MBq (for (161)Tb). The radiolabeling of cm09 was achieved in a greater than 96% radiochemical yield for all terbium radioisotopes. Biodistribution studies showed high and specific uptake in FR-positive tumor xenografts (23.8% ± 2.5% at 4 h after injection, 22.0% ± 4.4% at 24 h after injection, and 18.4% ± 1.8% at 48 h after injection). Excellent tumor-to-background ratios at 24 h after injection (tumor to blood, ≈ 15; tumor to liver, ≈ 5.9; and tumor to kidney, ≈ 0.8) allowed the visualization of tumors in mice using PET ((152)Tb-cm09) and SPECT ((155)Tb-cm09 and (161)Tb-cm09). Compared with no therapy, α- ((149)Tb-cm09) and β(-)-particle therapy ((161)Tb-cm09) resulted in a marked delay in tumor growth or even complete remission (33% for (149)Tb-cm09 and 80% for (161)Tb-cm09) and a significantly increased survival. CONCLUSION: For the first time, to our knowledge, 4 terbium radionuclides have been tested in parallel with tumor-bearing mice using an FR targeting agent. Along with excellent tumor visualization enabled by (152)Tb PET and (155)Tb SPECT, we demonstrated the therapeutic efficacy of the α-emitter (149)Tb and β(-)-emitter (161)Tb.

The fusion-evaporation reaction $^{244}\mathrm{Pu}(^{48}\mathrm{Ca},3\mathrm{\text{\ensuremath{-}}}4n)^{288,289}114$ was studied at the new gas-filled recoil separator TASCA. Thirteen correlated decay chains were observed and assigned to the production and decay of $^{288,289}114$. At a compound nucleus excitation energy of ${E}^{*}=39.8--43.9\text{ }\text{ }\mathrm{MeV}$, the $4n$ evaporation channel cross section was ${9.8}_{\ensuremath{-}3.1}^{+3.9}\text{ }\text{ }\mathrm{pb}$. At ${E}^{*}=36.1--39.5\text{ }\text{ }\mathrm{MeV}$, that of the $3n$ evaporation channel was ${8.0}_{\ensuremath{-}4.5}^{+7.4}\text{ }\text{ }\mathrm{pb}$. In one of the $3n$ evaporation channel decay chains, a previously unobserved $\ensuremath{\alpha}$ branch in $^{281}\mathrm{Ds}$ was observed (probability to be of random origin from background: 0.1%). This $\ensuremath{\alpha}$ decay populated the new nucleus $^{277}\mathrm{Hs}$, which decayed by spontaneous fission after a lifetime of 4.5 ms.